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Recent advances in exercise pressor reflex function in health and disease

      Abstract

      Autonomic alterations at the onset of exercise are critical to redistribute cardiac output towards the contracting muscles while preventing a fall in arterial pressure due to excessive vasodilation within the contracting muscles. Neural mechanisms responsible for these adjustments include central command, the exercise pressor reflex, and arterial and cardiopulmonary baroreflexes. The exercise pressor reflex evokes reflex increases in sympathetic activity to the heart and systemic vessels and decreases in parasympathetic activity to the heart, which increases blood pressure (BP), heart rate, and total peripheral resistance through vasoconstriction of systemic vessels. In this review, we discuss recent advancements in our understanding of exercise pressor reflex function in health and disease. Specifically, we discuss emerging evidence suggesting that sympathetic vasoconstrictor drive to the contracting and non-contracting skeletal muscle is differentially controlled by central command and the metaboreflex in healthy conditions. Further, we discuss evidence from animal and human studies showing that cardiovascular diseases, including hypertension, diabetes, and heart failure, lead to an altered exercise pressor reflex function. We also provide an update on the mechanisms thought to underlie this altered exercise pressor reflex function in each of these diseases. Although these mechanisms are complex, multifactorial, and dependent on the etiology of the disease, there is a clear consensus that several mechanisms are involved. Ultimately, approaches targeting these mechanisms are clinically significant as they provide alternative therapeutic strategies to prevent adverse cardiovascular events while also reducing symptoms of exercise intolerance.

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      References

        • Adams J.M.
        • Madden C.J.
        • Sved A.F.
        • Stocker S.D.
        Increased dietary salt enhances sympathoexcitatory and sympathoinhibitory responses from the rostral ventrolateral medulla.
        Hypertension. 2007; 50: 354-359
        • Adams J.M.
        • Bardgett M.E.
        • Stocker S.D.
        Ventral lamina terminalis mediates enhanced cardiovascular responses of rostral ventrolateral medulla neurons during increased dietary salt.
        Hypertension. 2009; 54: 308-314
        • Adreani C.M.
        • Kaufman M.P.
        Effect of arterial occlusion on responses of group III and IV afferents to dynamic exercise.
        J. Appl. Physiol. 1998; 84: 1827-1833
        • Adreani C.M.
        • Hill J.M.
        • Kaufman M.P.
        Responses of group III and IV muscle afferents to dynamic exercise.
        J. Appl. Physiol. 1997; 82: 1811-1817
        • Alam M.
        • Smirk F.H.
        Observation in man upon a blood pressure raising reflex arising from the voluntary muscles.
        J.Physiol. 1937; 89: 372-383
        • Alam M.
        • Smirk F.H.
        Observation in man concerning the effects of different types of sensory stimulation upon the blood pressure.
        Clin.Sci. 1938; 3: 253-258
        • Amann M.
        Significance of Group III and IV muscle afferents for the endurance exercising human.
        Clin. Exp. Pharmacol. Physiol. 2012; 39: 831-835
        • Amann M.
        • Proctor L.T.
        • Sebranek J.J.
        • Pegelow D.F.
        • Dempsey J.A.
        Opioid-mediated muscle afferents inhibit central motor drive and limit peripheral muscle fatigue development in humans.
        J. Physiol. 2009; 587: 271-283
        • Amann M.
        • Blain G.M.
        • Proctor L.T.
        • Sebranek J.J.
        • Pegelow D.F.
        • Dempsey J.A.
        Group III and IV muscle afferents contribute to ventilatory and cardiovascular response to rhythmic exercise in humans.
        J. Appl. Physiol. 2010; 109: 966-976
        • Amann M.
        • Runnels S.
        • Morgan D.E.
        • Trinity J.D.
        • Fjeldstad A.S.
        • Wray D.W.
        • Reese V.R.
        • Richardson R.S.
        On the contribution of group III and IV muscle afferents to the circulatory response to rhythmic exercise in humans.
        J. Physiol. 2011; 589: 3855-3866
        • Amann M.
        • Venturelli M.
        • Ives S.J.
        • Morgan D.E.
        • Gmelch B.
        • Witman M.A.
        • Jonathan Groot H.
        • Walter Wray D.
        • Stehlik J.
        • Richardson R.S.
        Group III/IV muscle afferents impair limb blood in patients with chronic heart failure.
        Int. J. Cardiol. 2014; 174: 368-375
        • Andrade D.C.
        • Arce-Alvarez A.
        • Toledo C.
        • Diaz H.S.
        • Lucero C.
        • Quintanilla R.A.
        • Schultz H.D.
        • Marcus N.J.
        • Amann M.
        • Del Rio R.
        Revisiting the physiological effects of exercise training on autonomic regulation and chemoreflex control in heart failure: does ejection fraction matter?.
        Am. J. Physiol. Heart Circ. Physiol. 2018; 314: H464-H474
        • Ansorge E.J.
        • Augustyniak R.A.
        • Perinot M.L.
        • Hammond R.L.
        • Kim J.K.
        • Sala-Mercado J.A.
        • Rodriguez J.
        • Rossi N.F.
        • O’Leary D.S.
        Altered muscle metaboreflex control of coronary blood flow and ventricular function in heart failure.
        Am. J. Physiol. Heart Circ. Physiol. 2005; 288: H1381-H1388
        • Antunes-Correa L.M.
        • Nobre T.S.
        • Groehs R.V.
        • Alves M.J.
        • Fernandes T.
        • Couto G.K.
        • Rondon M.U.
        • Oliveira P.
        • Lima M.
        • Mathias W.
        • Brum P.C.
        • Mady C.
        • Almeida D.R.
        • Rossoni L.V.
        • Oliveira E.M.
        • Middlekauff H.R.
        • Negrao C.E.
        Molecular basis for the improvement in muscle metaboreflex and mechanoreflex control in exercise-trained humans with chronic heart failure.
        Am. J. Physiol. Heart Circ. Physiol. 2014; 307: H1655-H1666
        • Baccelli G.
        • Reggiani P.
        • Mattioli A.
        • Corbellini E.
        • Garducci S.
        • Catalano M.
        The exercise pressor reflex and changes in radial arterial pressure and heart rate during walking in patients with arteriosclerosis obliterans.
        Angiology. 1999; 50: 361-374
        • Bagriantsev S.N.
        • Gracheva E.O.
        • Gallagher P.G.
        Piezo proteins: regulators of mechanosensation and other cellular processes.
        J. Biol. Chem. 2014; 289: 31673-31681
        • Barbosa T.C.
        • Vianna L.C.
        • Fernandes I.A.
        • Prodel E.
        • Rocha H.N.
        • Garcia V.P.
        • Rocha N.G.
        • Secher N.H.
        • Nobrega A.C.
        Intrathecal fentanyl abolishes the exaggerated blood pressure response to cycling in hypertensive men.
        J. Physiol. 2016; 594: 715-725
        • Barretto A.C.
        • Santos A.C.
        • Munhoz R.
        • Rondon M.U.
        • Franco F.G.
        • Trombetta I.C.
        • Roveda F.
        • de Matos L.N.
        • Braga A.M.
        • Middlekauff H.R.
        • Negrao C.E.
        Increased muscle sympathetic nerve activity predicts mortality in heart failure patients.
        Int. J. Cardiol. 2009; 135: 302-307
        • Bevegard B.S.
        • Shepherd J.T.
        Circulatory effects of stimulating the carotid arterial stretch receptors in man at rest and during exercise.
        J. Clin. Invest. 1966; 45: 132-142
        • Bock J.
        • Hughes W.
        • Ueda K.
        • Feider A.
        • Hanada S.
        • Kruse N.
        • Iwamoto E.
        • Casey D.
        Greater α1- and α2-adrenergic mediated vasoconstriction in contracting skeletal muscle of type 2 diabetic humans.
        FASEB J. 2019; 33: 696.619
        • Bommer C.
        • Heesemann E.
        • Sagalova V.
        • Manne-Goehler J.
        • Atun R.
        • Barnighausen T.
        • Vollmer S.
        The global economic burden of diabetes in adults aged 20–79 years: a cost-of-illness study.
        Lancet Diabetes Endocrinol. 2017; 5: 423-430
        • Boulton D.
        • Taylor C.E.
        • Macefield V.G.
        • Green S.
        Effect of contraction intensity on sympathetic nerve activity to active human skeletal muscle.
        Front. Physiol. 2014; 5: 194
        • Boulton D.
        • Taylor C.E.
        • Macefield V.G.
        • Green S.
        Contributions of central command and muscle feedback to sympathetic nerve activity in contracting human skeletal muscle.
        Front. Physiol. 2016; 7: 163
        • Boulton D.
        • Taylor C.E.
        • Green S.
        • Macefield V.G.
        The metaboreflex does not contribute to the increase in muscle sympathetic nerve activity to contracting muscle during static exercise in humans.
        J. Physiol. 2018; 596: 1091-1102
        • Boulton D.
        • Green S.
        • Macefield V.G.
        • Taylor C.E.
        A comparison of muscle sympathetic nerve activity to non-contracting muscle during isometric exercise in the upper and lower limbs.
        Front. Neurosci. 2019; 13: 341
        • Boyle J.P.
        • Honeycutt A.A.
        • Narayan K.M.
        • Hoerger T.J.
        • Geiss L.S.
        • Chen H.
        • Thompson T.J.
        Projection of diabetes burden through 2050: impact of changing demography and disease prevalence in the U.S.
        Diabetes Care. 2001; 24: 1936-1940
        • Broxterman R.M.
        • Hureau T.J.
        • Layec G.
        • Morgan D.E.
        • Bledsoe A.D.
        • Jessop J.E.
        • Amann M.
        • Richardson R.S.
        Influence of group III/IV muscle afferents on small muscle mass exercise performance: a bioenergetics perspective.
        J. Physiol. 2018; 596: 2301-2314
        • Bruce R.M.
        • Turner A.
        • White M.J.
        Ventilatory responses to muscle metaboreflex activation in chronic obstructive pulmonary disease.
        J. Physiol. 2016; 594: 6025-6035
        • Campos M.O.
        • Mansur D.E.
        • Mattos J.D.
        • Paiva A.C.S.
        • Videira R.L.R.
        • Macefield V.G.
        • da Nobrega A.C.L.
        • Fernandes I.A.
        Acid-sensing ion channels blockade attenuates pressor and sympathetic responses to skeletal muscle metaboreflex activation in humans.
        J. Appl. Physiol. 2019; 127: 1491-1501
        • Carretero O.A.
        • Oparil S.
        Essential hypertension. Part I: definition and etiology.
        Circulation. 2000; 101: 329-335
        • Chant B.
        • Bakali M.
        • Hinton T.
        • Burchell A.E.
        • Nightingale A.K.
        • Paton J.F.R.
        • Hart E.C.
        Antihypertensive treatment fails to control blood pressure during exercise.
        Hypertension. 2018; 72: 102-109
        • Coats A.J.
        • Clark A.L.
        • Piepoli M.
        • Volterrani M.
        • Poole-Wilson P.A.
        Symptoms and quality of life in heart failure: the muscle hypothesis.
        Br. Heart J. 1994; 72: S36-S39
        • Coote J.H.
        • Hilton S.M.
        • Perez-Gonzalez J.F.
        The reflex nature of the pressor response to muscular exercise.
        J. Physiol. 1971; 215: 789-804
        • Copp S.W.
        • Kim J.S.
        • Ruiz-Velasco V.
        • Kaufman M.P.
        The mechano-gated channel inhibitor GsMTx4 reduces the exercise pressor reflex in decerebrate rats.
        J. Physiol. 2016; 594: 641-655
        • Copp S.W.
        • Kim J.S.
        • Ruiz-Velasco V.
        • Kaufman M.P.
        The mechano-gated channel inhibitor GsMTx4 reduces the exercise pressor reflex in rats with ligated femoral arteries.
        Am. J. Physiol. Heart Circ. Physiol. 2016; 310: H1233-H1241
        • Corbett J.L.
        • Frankel H.L.
        • Harris P.J.
        Cardiovascular changes associated with skeletal muscle spasm in tetraplegic man.
        J. Physiol. 1971; 215: 381-393
        • Coutsos M.
        • Sala-Mercado J.A.
        • Ichinose M.
        • Li Z.
        • Dawe E.J.
        • O’Leary D.S.
        Muscle metaboreflex-induced coronary vasoconstriction limits ventricular contractility during dynamic exercise in heart failure.
        Am. J. Physiol. Heart Circ. Physiol. 2013; 304: H1029-H1037
        • Crisafulli A.
        • Salis E.
        • Tocco F.
        • Melis F.
        • Milia R.
        • Pittau G.
        • Caria M.A.
        • Solinas R.
        • Meloni L.
        • Pagliaro P.
        • Concu A.
        Impaired central hemodynamic response and exaggerated vasoconstriction during muscle metaboreflex activation in heart failure patients.
        Am. J. Physiol. Heart Circ. Physiol. 2007; 292: H2988-H2996
        • Cristina-Oliveira M.
        • Meireles K.
        • Spranger M.D.
        • O’Leary D.S.
        • Roschel H.
        • Peçanha T.
        Clinical safety of blood flow-restricted training? A comprehensive review of altered muscle metaboreflex in cardiovascular disease during ischemic exercise.
        Am. J. Phys. Heart Circ. Phys. 2020; 318: H90-H109
        • Cui J.
        • Blaha C.
        • Moradkhan R.
        • Gray K.S.
        • Sinoway L.I.
        Muscle sympathetic nerve activity responses to dynamic passive muscle stretch in humans.
        J. Physiol. 2006; 576: 625-634
        • Cunha R.S.
        • Cabral A.M.
        • Vasquez E.C.
        Evidence that the autonomic nervous system plays a major role in the L-NAME-induced hypertension in conscious rats.
        Am. J. Hypertens. 1993; 6: 806-809
        • da Costa Rodrigues T.
        • Pecis M.
        • Azevedo M.J.
        • Esteves J.F.
        • Gross J.L.
        Ambulatory blood pressure monitoring and progression of retinopathy in normotensive, normoalbuminuric type 1 diabetic patients: a 6-year follow-up study.
        Diabetes Res. Clin. Pract. 2006; 74: 135-140
        • Del Rio R.
        • Marcus N.J.
        • Schultz H.D.
        Carotid chemoreceptor ablation improves survival in heart failure: rescuing autonomic control of cardiorespiratory function.
        J. Am. Coll. Cardiol. 2013; 62: 2422-2430
        • Delaney E.P.
        • Greaney J.L.
        • Edwards D.G.
        • Rose W.C.
        • Fadel P.J.
        • Farquhar W.B.
        Exaggerated sympathetic and pressor responses to handgrip exercise in older hypertensive humans: role of the muscle metaboreflex.
        Am. J. Physiol. Heart Circ. Physiol. 2010; 299: H1318-H1327
        • Delliaux S.
        • Brerro-Saby C.
        • Steinberg J.G.
        • Jammes Y.
        Reactive oxygen species activate the group IV muscle afferents in resting and exercising muscle in rats.
        Pflugers Arch. 2009; 459: 143-150
        • Dombrowski M.
        • Mannozzi J.
        • O’Leary D.S.
        Neural control of cardiovascular function during exercise in hypertension.
        Front. Physiol. 2018; 9: 1829
        • Drew R.C.
        • Blaha C.A.
        • Herr M.D.
        • Cui R.
        • Sinoway L.I.
        Muscle mechanoreflex activation via passive calf stretch causes renal vasoconstriction in healthy humans.
        American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2017; 312: R956-R964
        • Ducrocq G.P.
        • Estrada J.A.
        • Kim J.S.
        • Kaufman M.P.
        Blocking the transient receptor potential vanilloid-1 does not reduce the exercise pressor reflex in healthy rats.
        American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2019; 317: R576-R587
        • Duvernoy C.S.
        • Raffel D.M.
        • Swanson S.D.
        • Jaiswal M.
        • Mueller G.
        • Ibrahim E.S.
        • Pennathur S.
        • Plunkett C.
        • Stojanovska J.
        • Brown M.B.
        • Pop-Busui R.
        Left ventricular metabolism, function, and sympathetic innervation in men and women with type 1 diabetes.
        J. Nucl. Cardiol. 2016; 23: 960-969
        • Eijkelkamp N.
        • Linley J.E.
        • Torres J.M.
        • Bee L.
        • Dickenson A.H.
        • Gringhuis M.
        • Minett M.S.
        • Hong G.S.
        • Lee E.
        • Oh U.
        • Ishikawa Y.
        • Zwartkuis F.J.
        • Cox J.J.
        • Wood J.N.
        A role for Piezo2 in EPAC1-dependent mechanical allodynia.
        Nat. Commun. 2013; 4: 1682
        • Eldridge F.L.
        • Millhorn D.E.
        • Waldrop T.G.
        Exercise hyperpnea and locomotion: parallel activation from the hypothalamus.
        Science. 1981; 211: 844-846
        • Eldridge F.L.
        • Millhorn D.E.
        • Kiley J.P.
        • Waldrop T.G.
        Stimulation by central command of locomotion, respiration and circulation during exercise.
        Respir. Physiol. 1985; 59: 313-337
        • Eshima K.
        • Hirooka Y.
        • Shigematsu H.
        • Matsuo I.
        • Koike G.
        • Sakai K.
        • Takeshita A.
        Angiotensin in the nucleus tractus solitarii contributes to neurogenic hypertension caused by chronic nitric oxide synthase inhibition.
        Hypertension. 2000; 36: 259-263
        • Fadel P.J.
        • Raven P.B.
        Human investigations into the arterial and cardiopulmonary baroreflexes during exercise.
        Exp. Physiol. 2012; 97: 39-50
        • Fadel P.J.
        • Farias Iii M.
        • Gallagher K.M.
        • Wang Z.
        • Thomas G.D.
        Oxidative stress and enhanced sympathetic vasoconstriction in contracting muscles of nitrate-tolerant rats and humans.
        J. Physiol. 2012; 590: 395-407
        • Fairfax S.T.
        • Padilla J.
        • Vianna L.C.
        • Davis M.J.
        • Fadel P.J.
        Spontaneous bursts of muscle sympathetic nerve activity decrease leg vascular conductance in resting humans.
        Am. J. Physiol. Heart Circ. Physiol. 2013; 304: H759-H766
        • Fanelli C.
        • Zatz R.
        Linking oxidative stress, the renin-angiotensin system, and hypertension.
        Hypertension. 2011; 57: 373-374
        • Farquhar W.B.
        • Wenner M.M.
        • Delaney E.P.
        • Prettyman A.V.
        • Stillabower M.E.
        Sympathetic neural responses to increased osmolality in humans.
        Am. J. Physiol. Heart Circ. Physiol. 2006; 291: H2181-H2186
        • Fermo E.
        • Vercellati C.
        • Marcello A.P.
        • Zaninoni A.
        • van Wijk R.
        • Mirra N.
        • Curcio C.
        • Cortelezzi A.
        • Zanella A.
        • Barcellini W.
        • Bianchi P.
        Hereditary xerocytosis due to mutations in PIEZO1 gene associated with heterozygous pyruvate kinase deficiency and beta-thalassemia trait in two unrelated families.
        Case Rep Hematol. 2017; 2017: 2769570
        • Ferreira L.F.
        • Laitano O.
        Regulation of NADPH oxidases in skeletal muscle.
        Free Radic. Biol. Med. 2016; 98: 18-28
        • Flaa A.
        • Mundal H.H.
        • Eide I.
        • Kjeldsen S.
        • Rostrup M.
        Sympathetic activity and cardiovascular risk factors in young men in the low, normal, and high blood pressure ranges.
        Hypertension. 2006; 47: 396-402
        • Floras J.S.
        Clinical aspects of sympathetic activation and parasympathetic withdrawal in heart failure.
        J. Am. Coll. Cardiol. 1993; 22: 72A-84A
        • Frisbee J.C.
        • Lewis M.T.
        • Kasper J.D.
        • Chantler P.D.
        • Wiseman R.W.
        Type 2 diabetes mellitus in the Goto-Kakizaki rat impairs microvascular function and contributes to premature skeletal muscle fatigue.
        J. Appl. Physiol. 2019; 126: 626-637
        • Fryar C.D.
        • Ostchega Y.
        • Hales C.M.
        • Zhang G.
        • Kruszon-Moran D.
        Hypertension prevalence and control among adults: United States, 2015–2016.
        NCHS Data Brief. 2017; : 1-8
        • Gao L.
        • Wang W.
        • Li Y.L.
        • Schultz H.D.
        • Liu D.
        • Cornish K.G.
        • Zucker I.H.
        Superoxide mediates sympathoexcitation in heart failure: roles of angiotensin II and NAD(P)H oxidase.
        Circ. Res. 2004; 95: 937-944
        • Gao Z.
        • Xing J.
        • Sinoway L.
        • Li J.
        P2X receptor-mediated muscle pressor reflex in myocardial infarction.
        Am. J. Physiol. Heart Circ. Physiol. 2007; 292: H939-H945
        • Goodwin G.M.
        • McCloskey D.I.
        • Mitchell J.H.
        Cardiovascular and respiratory responses to changes in central command during isometric exercise at constant muscle tension.
        J.Physiol.(Lond.). 1972; 226: 173-190
        • Grassi G.
        • Dell'Oro R.
        • Seravalle G.
        • Foglia G.
        • Trevano F.Q.
        • Mancia G.
        Short- and long-term neuroadrenergic effects of moderate dietary sodium restriction in essential hypertension.
        Circulation. 2002; 106: 1957-1961
        • Greaney J.L.
        • DuPont J.J.
        • Lennon-Edwards S.L.
        • Sanders P.W.
        • Edwards D.G.
        • Farquhar W.B.
        Dietary sodium loading impairs microvascular function independent of blood pressure in humans: role of oxidative stress.
        J. Physiol. 2012; 590: 5519-5528
        • Greaney J.L.
        • Matthews E.L.
        • Boggs M.E.
        • Edwards D.G.
        • Duncan R.L.
        • Farquhar W.B.
        Exaggerated exercise pressor reflex in adults with moderately elevated systolic blood pressure: role of purinergic receptors.
        Am. J. Physiol. Heart Circ. Physiol. 2014; 306: H132-H141
        • Greaney J.L.
        • Edwards D.G.
        • Fadel P.J.
        • Farquhar W.B.
        Rapid onset pressor and sympathetic responses to static handgrip in older hypertensive adults.
        J. Hum. Hypertens. 2015; 29: 402-408
        • Groen M.B.
        • Knudsen T.A.
        • Finsen S.H.
        • Pedersen B.K.
        • Hellsten Y.
        • Mortensen S.P.
        Reduced skeletal-muscle perfusion and impaired ATP release during hypoxia and exercise in individuals with type 2 diabetes.
        Diabetologia. 2019; 62: 485-493
        • Grotle A.K.
        • Stone A.J.
        Exaggerated exercise pressor reflex in type 2 diabetes: potential role of oxidative stress.
        Autonomic Neuroscience: Basic & Clinical. 2019; 222: 102591
        • Grotle A.K.
        • Garcia E.A.
        • Huo Y.
        • Stone A.J.
        Temporal changes in the exercise pressor reflex in type 1 diabetic rats.
        Am. J. Physiol. Heart Circ. Physiol. 2017; 313: H708-H714
        • Grotle A.K.
        • Crawford C.K.
        • Huo Y.
        • Ybarbo K.M.
        • Harrison M.L.
        • Graham J.
        • Stanhope K.L.
        • Havel P.J.
        • Fadel P.J.
        • Stone A.J.
        Exaggerated cardiovascular responses to muscle contraction and tendon stretch in UCD type-2 diabetes mellitus rats.
        Am. J. Physiol. Heart Circ. Physiol. 2019; 317: H479-H486
        • Grotle A.K.
        • Garcia E.A.
        • Harrison M.L.
        • Huo Y.
        • Crawford C.K.
        • Ybarbo K.M.
        • Stone A.J.
        Exaggerated mechanoreflex in early-stage type 1 diabetic rats: role of Piezo channels.
        American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2019; 316: R417-R426
        • Guyenet P.G.
        Putative mechanism of salt-dependent neurogenic hypertension: cell-autonomous activation of organum vasculosum laminae terminalis neurons by hypernatremia.
        Hypertension. 2017; 69: 20-22
        • Hajduczok G.
        • Hade J.S.
        • Mark A.L.
        • Williams J.L.
        • Felder R.B.
        Central command increases sympathetic nerve activity during spontaneous locomotion in cats.
        Circ. Res. 1991; 69: 66-75
        • Hammond R.L.
        • Augustyniak R.A.
        • Rossi N.F.
        • Churchill P.C.
        • Lapanowski K.
        • O’Leary D.S.
        Heart failure alters the strength and mechanisms of the muscle metaboreflex.
        Am. J. Physiol. Heart Circ. Physiol. 2000; 278: H818-H828
        • Hammond R.L.
        • Augustyniak R.A.
        • Rossi N.F.
        • Lapanowski K.
        • Dunbar J.C.
        • O’Leary D.S.
        Alteration of humoral and peripheral vascular responses during graded exercise in heart failure.
        J. Appl. Physiol. 2001; 90: 55-61
        • Hansen J.
        • Thomas G.D.
        • Jacobsen T.N.
        • Victor R.G.
        Muscle metaboreflex triggers parallel sympathetic activation in exercising and resting human skeletal muscle.
        Am. J. Phys. 1994; 266: H2508-H2514
        • Harms J.E.
        • Kuczmarski J.M.
        • Kim J.S.
        • Thomas G.D.
        • Kaufman M.P.
        The role played by oxidative stress in evoking the exercise pressor reflex in health and simulated peripheral artery disease.
        J. Physiol. 2017; 595: 4365-4378
        • Hayes S.G.
        • Kaufman M.P.
        Gadolinium attenuates exercise pressor reflex in cats.
        Am. J. Physiol. Heart Circ. Physiol. 2001; 280: H2153-H2161
        • Hayes S.G.
        • McCord J.L.
        • Rainier J.
        • Liu Z.
        • Kaufman M.P.
        Role played by acid-sensitive ion channels in evoking the exercise pressor reflex.
        Am. J. Physiol. Heart Circ. Physiol. 2008; 295: H1720-H1725
        • Hayes S.G.
        • McCord J.L.
        • Koba S.
        • Kaufman M.P.
        Gadolinium inhibits group III but not group IV muscle afferent responses to dynamic exercise.
        J. Physiol. 2009; 587: 873-882
        • Hill J.M.
        • Adreani C.M.
        • Kaufman M.P.
        Muscle reflex stimulates sympathetic postganglionic efferents innervating triceps surae muscles of cats.
        Am. J. Phys. 1996; 271: H38-H43
        • Hirooka Y.
        Role of reactive oxygen species in brainstem in neural mechanisms of hypertension.
        Autonomic Neuroscience: Basic & Clinical. 2008; 142: 20-24
        • Hoberg E.
        • Schuler G.
        • Kunze B.
        • Obermoser A.-L.
        • Hauer K.
        • Mautner H.-P.
        • Schlierf G.
        • Kübler W.
        Silent myocardial ischemia as a potential link between lack of premonitoring symptoms and increased risk of cardiac arrest during physical stress.
        Am. J. Cardiol. 1990; 65: 583-589
        • Holwerda S.W.
        • Restaino R.M.
        • Manrique C.
        • Lastra G.
        • Fisher J.P.
        • Fadel P.J.
        Augmented pressor and sympathetic responses to skeletal muscle metaboreflex activation in type 2 diabetes patients.
        Am. J. Physiol. Heart Circ. Physiol. 2016; 310: H300-H309
        • Huang B.S.
        • Leenen F.H.
        Dietary Na and baroreflex modulation of blood pressure and RSNA in normotensive vs. spontaneously hypertensive rats.
        Am. J. Phys. 1994; 266: H496-H502
        • Hureau T.J.
        • Weavil J.C.
        • Thurston T.S.
        • Wan H.Y.
        • Gifford J.R.
        • Jessop J.E.
        • Buys M.J.
        • Richardson R.S.
        • Amann M.
        Pharmacological attenuation of group III/IV muscle afferents improves endurance performance when oxygen delivery to locomotor muscles is preserved.
        J. Appl. Physiol. 2019; 127: 1257-1266
        • Ishizawa R.
        • Kim H.K.
        • Hotta N.
        • Iwamoto G.A.
        • Vongpatanasin W.
        • Mitchell J.H.
        • Smith S.A.
        • Mizuno M.
        Skeletal muscle reflex-induced sympathetic dysregulation and sensitization of muscle afferents in type 1 diabetic rats.
        Hypertension. 2020; 75: 1072-1081
        • Ives S.J.
        • Amann M.
        • Venturelli M.
        • Witman M.A.
        • Groot H.J.
        • Wray D.W.
        • Morgan D.E.
        • Stehlik J.
        • Richardson R.S.
        The mechanoreflex and hemodynamic response to passive leg movement in heart failure.
        Med. Sci. Sports Exerc. 2016; 48: 368-376
        • Jänig W.
        Integrative Action of the Autonomic Nervous System.
        Cambridge University Press, Cambridge2006
        • Janig W.
        Mechanical allodynia generated by stimulation of unmyelinated afferent nerve fibres.
        J. Physiol. 2011; 589: 4407-4408
        • Kahn J.F.
        The static exercise-induced arterial hypertension test.
        Presse Med. 1991; 20: 1067-1071
        • Karavelioglu Y.
        • Karapinar H.
        • Gul I.
        • Kucukdurmaz Z.
        • Yilmaz A.
        • Akpek M.
        • Kaya M.G.
        Blood pressure response to exercise is exaggerated in normotensive diabetic patients.
        Blood Press. 2013; 22: 21-26
        • Kaufman M.P.
        • Hayes S.G.
        The exercise pressor reflex.
        Clin. Auton. Res. 2002; 12: 429-439
        • Kaufman M.P.
        • Longhurst J.C.
        • Rybicki K.J.
        • Wallach J.H.
        • Mitchell J.H.
        Effects of static muscular contraction on impulse activity of groups III and IV afferents in cats.
        J. Appl. Physiol. Respir. Environ. Exerc. Physiol. 1983; 55: 105-112
        • Kaufman M.P.
        • Rybicki K.J.
        • Waldrop T.G.
        • Ordway G.A.
        Effect of ischemia on responses of group III and IV afferents to contraction.
        J. Appl. Physiol. Respir. Environ. Exerc. Physiol. 1984; 57: 644-650
        • Kaur J.
        • Machado T.M.
        • Alvarez A.
        • Krishnan A.C.
        • Hanna H.W.
        • Altamimi Y.H.
        • Senador D.
        • Spranger M.D.
        • O’Leary D.S.
        Muscle metaboreflex activation during dynamic exercise vasoconstricts ischemic active skeletal muscle.
        Am. J. Physiol. Heart Circ. Physiol. 2015; 309: H2145-H2151
        • Kaur J.
        • Krishnan A.C.
        • Senador D.
        • Alvarez A.
        • Hanna H.W.
        • O’Leary D.S.
        Altered arterial baroreflex-muscle metaboreflex interaction in heart failure.
        Am. J. Physiol. Heart Circ. Physiol. 2018; 315: H1383-H1392
        • Kaur J.
        • Senador D.
        • Krishnan A.C.
        • Hanna H.W.
        • Alvarez A.
        • Machado T.M.
        • O’Leary D.S.
        Muscle metaboreflex-induced vasoconstriction in the ischemic active muscle is exaggerated in heart failure.
        Am. J. Physiol. Heart Circ. Physiol. 2018; 314: H11-H18
        • Kazatani Y.
        • Hamada M.
        • Shigematsu Y.
        • Hiwada K.
        • Kokubu T.
        Beneficial effect of a long-term antihypertensive therapy on blood pressure response to isometric handgrip exercise in patients with essential hypertension.
        Am. J. Ther. 1995; 2: 165-169
        • Khan G.M.
        • Chen S.R.
        • Pan H.L.
        Role of primary afferent nerves in allodynia caused by diabetic neuropathy in rats.
        Neuroscience. 2002; 114: 291-299
        • Kim J.K.
        • Augustyniak R.A.
        • Sala-Mercado J.A.
        • Hammond R.L.
        • Ansorge E.J.
        • Rossi N.F.
        • O’Leary D.S.
        Heart failure alters the strength and mechanisms of arterial baroreflex pressor responses during dynamic exercise.
        Am. J. Physiol. Heart Circ. Physiol. 2004; 287: H1682-H1688
        • Kim J.K.
        • Sala-Mercado J.A.
        • Rodriguez J.
        • Scislo T.J.
        • O’Leary D.S.
        Arterial baroreflex alters strength and mechanisms of muscle metaboreflex during dynamic exercise.
        Am. J. Physiol. Heart Circ. Physiol. 2005; 288: H1374-H1380
        • Kim J.K.
        • Hayes S.G.
        • Kindig A.E.
        • Kaufman M.P.
        Thin-fiber mechanoreceptors reflexly increase renal sympathetic nerve activity during static contraction.
        Am. J. Physiol. Heart Circ. Physiol. 2007; 292: H866-H873
        • Kim H.K.
        • Hotta N.
        • Ishizawa R.
        • Iwamoto G.A.
        • Vongpatanasin W.
        • Mitchell J.H.
        • Smith S.A.
        • Mizuno M.
        Exaggerated pressor and sympathetic responses to stimulation of the mesencephalic locomotor region and exercise pressor reflex in type 2 diabetic rats.
        American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2019; 317: R270-R279
        • Kim H.K.
        • Hotta N.
        • Ishizawa R.
        • Iwamoto G.A.
        • Vongpatanasin W.
        • Mitchell J.H.
        • Smith S.A.
        • Mizuno M.
        Exaggerated pressor and sympathetic responses to stimulation of the mesencephalic locomotor region and exercise pressor reflex in type II diabetic rats.
        American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2019; 317: R270-R279
        • Kindig A.E.
        • Heller T.B.
        • Kaufman M.P.
        VR-1 receptor blockade attenuates the pressor response to capsaicin but has no effect on the pressor response to contraction in cats.
        Am. J. Physiol. Heart Circ. Physiol. 2005; 288: H1867-H1873
        • Kindig A.E.
        • Hayes S.G.
        • Kaufman M.P.
        Blockade of purinergic 2 receptors attenuates the mechanoreceptor component of the exercise pressor reflex.
        Am. J. Physiol. Heart Circ. Physiol. 2007; 293: H2995-H3000
        • Kingwell B.A.
        • Formosa M.
        • Muhlmann M.
        • Bradley S.J.
        • McConell G.K.
        Type 2 diabetic individuals have impaired leg blood flow responses to exercise: role of endothelium-dependent vasodilation.
        Diabetes Care. 2003; 26: 899-904
        • Kinsman B.J.
        • Simmonds S.S.
        • Browning K.N.
        • Stocker S.D.
        Organum vasculosum of the lamina terminalis detects NaCl to elevate sympathetic nerve activity and blood pressure.
        Hypertension. 2017; 69: 163-170
        • Koba S.
        • Yoshida T.
        • Hayashi N.
        Renal sympathetic and circulatory responses to activation of the exercise pressor reflex in rats.
        Exp. Physiol. 2006; 91: 111-119
        • Koba S.
        • Xing J.
        • Sinoway L.I.
        • Li J.
        Differential sympathetic outflow elicited by active muscle in rats.
        Am. J. Physiol. Heart Circ. Physiol. 2007; 293: H2335-H2343
        • Koba S.
        • Xing J.
        • Sinoway L.I.
        • Li J.
        Sympathetic nerve responses to muscle contraction and stretch in ischemic heart failure.
        Am. J. Physiol. Heart Circ. Physiol. 2008; 294: H311-H321
        • Koba S.
        • Gao Z.
        • Sinoway L.I.
        Oxidative stress and the muscle reflex in heart failure.
        J. Physiol. 2009; 587: 5227-5237
        • Koba S.
        • Watanabe R.
        • Kano N.
        • Watanabe T.
        Oxidative stress exaggerates skeletal muscle contraction-evoked reflex sympathoexcitation in rats with hypertension induced by angiotensin II.
        Am. J. Physiol. Heart Circ. Physiol. 2013; 304: H142-H153
        • Kurl S.
        • Laukkanen J.A.
        • Rauramaa R.
        • Lakka T.A.
        • Sivenius J.
        • Salonen J.T.
        Systolic blood pressure response to exercise stress test and risk of stroke.
        Stroke. 2001; 32: 2036-2041
        • Lalande S.
        • Gusso S.
        • Hofman P.L.
        • Baldi J.C.
        Reduced leg blood flow during submaximal exercise in type 2 diabetes.
        Med. Sci. Sports Exerc. 2008; 40: 612-617
        • Lambert E.A.
        • Schlaich M.P.
        Reduced sympathoneural responses to the cold pressor test in individuals with essential hypertension and in those genetically predisposed to hypertension. No support for the “pressor reactor” hypothesis of hypertension development.
        Am. J. Hypertens. 2004; 17: 863-868
        • Laukkanen J.A.
        • Kurl S.
        • Rauramaa R.
        • Lakka T.A.
        • Venalainen J.M.
        • Salonen J.T.
        Systolic blood pressure response to exercise testing is related to the risk of acute myocardial infarction in middle-aged men.
        Eur J Cardiovasc Prev Rehabil. 2006; 13: 421-428
        • Leal A.K.
        • Williams M.A.
        • Garry M.G.
        • Mitchell J.H.
        • Smith S.A.
        Evidence for functional alterations in the skeletal muscle mechanoreflex and metaboreflex in hypertensive rats.
        Am. J. Physiol. Heart Circ. Physiol. 2008; 295: H1429-H1438
        • Leal A.K.
        • Murphy M.N.
        • Iwamoto G.A.
        • Mitchell J.H.
        • Smith S.A.
        A role for nitric oxide within the nucleus tractus solitarii in the development of muscle mechanoreflex dysfunction in hypertension.
        Exp. Physiol. 2012; 97: 1292-1304
        • Leal A.K.
        • Stone A.J.
        • Yamauchi K.
        • McCord J.L.
        • Kaufman M.P.
        Blockade of B2 receptors attenuates the responses of group III afferents to static contraction.
        Neurosci. Lett. 2013; 555: 231-236
        • Li J.
        • Potts J.T.
        NO formation in nucleus tractus solitarii attenuates pressor response evoked by skeletal muscle afferents.
        Am. J. Physiol. Heart Circ. Physiol. 2001; 280: H2371-H2379
        • Li J.
        • Sinoway A.N.
        • Gao Z.
        • Maile M.D.
        • Pu M.
        • Sinoway L.I.
        Muscle mechanoreflex and metaboreflex responses after myocardial infarction in rats.
        Circulation. 2004; 110: 3049-3054
        • Li J.
        • Gao Z.
        • Kehoe V.
        • Xing J.
        • King N.
        • Sinoway L.
        Interstitial adenosine triphosphate modulates muscle afferent nerve-mediated pressor reflex.
        Muscle Nerve. 2008; 38: 972-977
        • Lind A.R.
        • McNicol G.W.
        • Bruce R.A.
        • Macdonald H.R.
        • Donald K.W.
        The cardiovascular responses to sustained contractions of a patient with unilateral syringomyelia.
        Clin. Sci. 1968; 35: 45-53
        • Liu J.L.
        • Murakami H.
        • Sanderford M.
        • Bishop V.S.
        • Zucker I.H.
        ANG II and baroreflex function in rabbits with CHF and lesions of the area postrema.
        Am. J. Phys. 1999; 277: H342-H350
        • Lolignier S.
        • Eijkelkamp N.
        • Wood J.N.
        Mechanical allodynia.
        Pflugers Arch. 2015; 467: 133-139
        • Maahs D.M.
        • West N.A.
        • Lawrence J.M.
        • Mayer-Davis E.J.
        Epidemiology of type 1 diabetes.
        Endocrinol. Metab. Clin. N. Am. 2010; 39: 481-497
        • Magnani S.
        • Roberto S.
        • Sainas G.
        • Milia R.
        • Palazzolo G.
        • Cugusi L.
        • Pinna V.
        • Doneddu A.
        • Kakhak S.A.H.
        • Tocco F.
        • Mercuro G.
        • Crisafulli A.
        Metaboreflex-mediated hemodynamic abnormalities in individuals with coronary artery disease without overt signs or symptoms of heart failure.
        Am. J. Physiol. Heart Circ. Physiol. 2018; 314: H452-H463
        • Magnusson G.
        • Kaijser L.
        • Sylvén C.
        • Karlberg K.-E.
        • Isberg B.
        • Saltin B.
        Peak skeletal muscle perfusion is maintained in patients with chronic heart failure when only a small muscle mass is exercised.
        Cardiovasc. Res. 1997; 33: 297-306
        • Mark A.L.
        • Victor R.G.
        • Nerhed C.
        • Wallin B.G.
        Microneurographic studies of the mechanisms of sympathetic nerve responses to static exercise in humans.
        Circ. Res. 1985; 57: 461-469
        • Matsukawa T.
        • Gotoh E.
        • Uneda S.
        • Miyajima E.
        • Shionoiri H.
        • Tochikubo O.
        • Ishii M.
        Augmented sympathetic nerve activity in response to stressors in young borderline hypertensive men.
        Acta Physiol. Scand. 1991; 141: 157-165
        • Matteucci E.
        • Rosada J.
        • Pinelli M.
        • Giusti C.
        • Giampietro O.
        Systolic blood pressure response to exercise in type 1 diabetes families compared with healthy control individuals.
        J. Hypertens. 2006; 24: 1745-1751
        • Mayer-Davis E.J.
        • Dabelea D.
        • Lawrence J.M.
        Incidence trends of type 1 and type 2 diabetes among youths, 2002–2012.
        N. Engl. J. Med. 2017; 377: 301
        • McCloskey D.I.
        • Mitchell J.H.
        Reflex cardiovascular and respiratory responses originating in exercising muscle.
        J. Physiol. 1972; 224: 173-186
        • McCord J.L.
        • Tsuchimochi H.
        • Kaufman M.P.
        P2X2/3 and P2X3 receptors contribute to the metaboreceptor component of the exercise pressor reflex.
        J. Appl. Physiol. 2010; 109: 1416-1423
        • McIlveen S.A.
        • Hayes S.G.
        • Kaufman M.P.
        Both central command and exercise pressor reflex reset carotid sinus baroreflex.
        Am. J. Physiol. Heart Circ. Physiol. 2001; 280: H1454-H1463
        • Meintjes A.F.
        • Nobrega A.C.
        • Fuchs I.E.
        • Ally A.
        • Wilson L.B.
        Attenuation of the exercise pressor reflex. Effect of opioid agonist on substance P release in L-7 dorsal horn of cats.
        Circ. Res. 1995; 77: 326-334
        • Metra M.
        • Teerlink J.R.
        Heart failure.
        Lancet. 2017; 390: 1981-1995
        • Middlekauff H.R.
        • Chiu J.
        Cyclooxygenase products sensitize muscle mechanoreceptors in healthy humans.
        Am. J. Physiol. Heart Circ. Physiol. 2004; 287: H1944-H1949
        • Middlekauff H.R.
        • Sinoway L.I.
        Increased mechanoreceptor stimulation explains the exaggerated exercise pressor reflex seen in heart failure.
        J. Appl. Physiol. 2007; 102 (discussion 496): 492-494
        • Middlekauff H.R.
        • Nitzsche E.U.
        • Hoh C.K.
        • Hamilton M.A.
        • Fonarow G.C.
        • Hage A.
        • Moriguchi J.D.
        Exaggerated muscle mechanoreflex control of reflex renal vasoconstriction in heart failure.
        J. Appl. Physiol. 2001; 90: 1714-1719
        • Middlekauff H.R.
        • Chiu J.
        • Hamilton M.A.
        • Fonarow G.C.
        • Maclellan W.R.
        • Hage A.
        • Moriguchi J.
        • Patel J.
        Muscle mechanoreceptor sensitivity in heart failure.
        Am. J. Physiol. Heart Circ. Physiol. 2004; 287: H1937-H1943
        • Migdal K.U.
        • Babcock M.C.
        • Robinson A.T.
        • Watso J.C.
        • Wenner M.M.
        • Stocker S.D.
        • Farquhar W.B.
        The impact of high dietary sodium consumption on blood pressure variability in healthy, young adults.
        Am. J. Hypertens. 2020; 33: 422-429
        • Mitchell J.H.
        Abnormal cardiovascular response to exercise in hypertension: contribution of neural factors.
        American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2017; 312: R851-R863
        • Mittleman M.A.
        • Siscovick D.S.
        Physical exertion as a trigger of myocardial infarction and sudden cardiac death.
        Cardiol. Clin. 1996; 14: 263-270
        • Mittleman M.A.
        • Maclure M.
        • Tofler G.H.
        • Sherwood J.B.
        • Goldberg R.J.
        • Muller J.E.
        Triggering of acute myocardial infarction by heavy physical exertion. Protection against triggering by regular exertion. Determinants of Myocardial Infarction Onset Study Investigators.
        N. Engl. J. Med. 1993; 329: 1677-1683
        • Mizuno M.
        • Murphy M.N.
        • Mitchell J.H.
        • Smith S.A.
        Antagonism of the TRPv1 receptor partially corrects muscle metaboreflex overactivity in spontaneously hypertensive rats.
        J. Physiol. 2011; 589: 6191-6204
        • Mizuno M.
        • Murphy M.N.
        • Mitchell J.H.
        • Smith S.A.
        Skeletal muscle reflex-mediated changes in sympathetic nerve activity are abnormal in spontaneously hypertensive rats.
        Am. J. Physiol. Heart Circ. Physiol. 2011; 300: H968-H977
        • Mizuno M.
        • Siddique K.
        • Baum M.
        • Smith S.A.
        Prenatal programming of hypertension induces sympathetic overactivity in response to physical stress.
        Hypertension. 2013; 61: 180-186
        • Mizuno M.
        • Iwamoto G.A.
        • Vongpatanasin W.
        • Mitchell J.H.
        • Smith S.A.
        Exercise training improves functional sympatholysis in spontaneously hypertensive rats through a nitric oxide-dependent mechanism.
        Am. J. Physiol. Heart Circ. Physiol. 2014; 307: H242-H251
        • Mizuno M.
        • Mitchell J.H.
        • Crawford S.
        • Huang C.L.
        • Maalouf N.
        • Hu M.C.
        • Moe O.W.
        • Smith S.A.
        • Vongpatanasin W.
        High dietary phosphate intake induces hypertension and augments exercise pressor reflex function in rats.
        American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2016; 311: R39-R48
        • Molliver D.C.
        • Immke D.C.
        • Fierro L.
        • Pare M.
        • Rice F.L.
        • McCleskey E.W.
        ASIC3, an acid-sensing ion channel, is expressed in metaboreceptive sensory neurons.
        Mol. Pain. 2005; 1: 35
        • Morales A.
        • Gao W.
        • Lu J.
        • Xing J.
        • Li J.
        Muscle cyclo-oxygenase-2 pathway contributes to the exaggerated muscle mechanoreflex in rats with congestive heart failure.
        Exp. Physiol. 2012; 97: 943-954
        • Mousa T.M.
        • Liu D.
        • Cornish K.G.
        • Zucker I.H.
        Exercise training enhances baroreflex sensitivity by an angiotensin II-dependent mechanism in chronic heart failure.
        J. Appl. Physiol. 2008; 104: 616-624
        • Mueller S.M.
        Adult sympathetic and vascular dysfunction in experimental juvenile-onset diabetes mellitus.
        Microvasc. Res. 1984; 28: 75-86
        • Mueller S.M.
        • Mueller T.M.
        • Ertel P.J.
        Sympathetic and vascular dysfunction in early experimental juvenile diabetes mellitus.
        Am. J. Phys. 1982; 243: H139-H144
        • Muller M.D.
        • Drew R.C.
        • Blaha C.A.
        • Mast J.L.
        • Cui J.
        • Reed A.B.
        • Sinoway L.I.
        Oxidative stress contributes to the augmented exercise pressor reflex in peripheral arterial disease patients.
        J. Physiol. 2012; 590: 6237-6246
        • Murphy M.N.
        • Mizuno M.
        • Downey R.M.
        • Squiers J.J.
        • Squiers K.E.
        • Smith S.A.
        Neuronal nitric oxide synthase expression is lower in areas of the nucleus tractus solitarius excited by skeletal muscle reflexes in hypertensive rats.
        Am. J. Physiol. Heart Circ. Physiol. 2013; 304: H1547-H1557
        • Negrao C.E.
        • Rondon M.U.
        • Tinucci T.
        • Alves M.J.
        • Roveda F.
        • Braga A.M.
        • Reis S.F.
        • Nastari L.
        • Barretto A.C.
        • Krieger E.M.
        • Middlekauff H.R.
        Abnormal neurovascular control during exercise is linked to heart failure severity.
        Am. J. Physiol. Heart Circ. Physiol. 2001; 280: H1286-H1292
        • Negrão C.E.
        • Trombetta I.C.
        • Batalha L.T.
        • Ribeiro M.M.
        • Rondon M.U.P.B.
        • Tinucci T.
        • Forjaz C.L.M.
        • Barretto A.C.P.
        • Halpern A.
        • Villares S.M.F.
        Muscle metaboreflex control is diminished in normotensive obese women.
        Am. J. Phys. Heart Circ. Phys. 2001; 281: H469-H475
        • Norton K.H.
        • Boushel R.
        • Strange S.
        • Saltin B.
        • Raven P.B.
        Resetting of the carotid arterial baroreflex during dynamic exercise in humans.
        J. Appl. Physiol. 1999; 87: 332-338
        • Notarius C.F.
        • Atchison D.J.
        • Floras J.S.
        Impact of heart failure and exercise capacity on sympathetic response to handgrip exercise.
        Am. J. Physiol. Heart Circ. Physiol. 2001; 280: H969-H976
        • Noubiap J.J.
        • Nansseu J.R.
        • Nyaga U.F.
        • Sime P.S.
        • Francis I.
        • Bigna J.J.
        Global prevalence of resistant hypertension: a meta-analysis of data from 3.2 million patients.
        Heart. 2019; 105: 98-105
        • O’Connor E.
        • Green S.
        • Kiely C.
        • O’Shea D.
        • Egana M.
        Differential effects of age and type 2 diabetes on dynamic vs. peak response of pulmonary oxygen uptake during exercise.
        J. Appl. Physiol. 2015; 118: 1031-1039
        • Oguri M.
        • Adachi H.
        • Ohno T.
        • Oshima S.
        • Kurabayashi M.
        Effect of a single bout of moderate exercise on glucose uptake in type 2 diabetes mellitus.
        J. Cardiol. 2009; 53: 8-14
        • O’Leary D.S.
        • Augustyniak R.A.
        Muscle metaboreflex increases ventricular performance in conscious dogs.
        Am. J. Phys. 1998; 275: H220-H224
        • O’Leary D.S.
        • Robinson E.D.
        • Butler J.L.
        Is active skeletal muscle functionally vasoconstricted during dynamic exercise in conscious dogs?.
        Am. J. Phys. Regul. Integr. Comp. Phys. 1997; 272: R386-R391
        • O’Leary D.S.
        • Augustyniak R.A.
        • Ansorge E.J.
        • Collins H.L.
        Muscle metaboreflex improves O2delivery to ischemic active skeletal muscle.
        Am. J. Phys. Heart Circ. Phys. 1999; 276: H1399-H1403
        • O’Leary D.S.
        • Augustyniak R.A.
        • Ansorge E.J.
        • Collins H.L.
        Muscle metaboreflex improves O2 delivery to ischemic active skeletal muscle.
        Am. J. Phys. 1999; 276: H1399-H1403
        • Orstavik K.
        • Namer B.
        • Schmidt R.
        • Schmelz M.
        • Hilliges M.
        • Weidner C.
        • Carr R.W.
        • Handwerker H.
        • Jorum E.
        • Torebjork H.E.
        Abnormal function of C-fibers in patients with diabetic neuropathy.
        J. Neurosci. 2006; 26: 11287-11294
        • Pan H.L.
        • Stebbins C.L.
        • Longhurst J.C.
        Bradykinin contributes to the exercise pressor reflex: mechanism of action.
        J. Appl. Physiol. 1993; 75: 2061-2068
        • Park J.
        • Campese V.M.
        • Middlekauff H.R.
        Exercise pressor reflex in humans with end-stage renal disease.
        American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2008; 295: R1188-R1194
        • Park S.P.
        • Kim B.M.
        • Koo J.Y.
        • Cho H.
        • Lee C.H.
        • Kim M.
        • Na H.S.
        • Oh U.
        A tarantula spider toxin, GsMTx4, reduces mechanical and neuropathic pain.
        Pain. 2008; 137: 208-217
        • Pawloski-Dahm C.M.
        • Gordon F.J.
        Increased dietary salt sensitizes vasomotor neurons of the rostral ventrolateral medulla.
        Hypertension. 1993; 22: 929-933
        • Pickar J.G.
        • Hill J.M.
        • Kaufman M.P.
        Dynamic exercise stimulates group III muscle afferents.
        J. Neurophysiol. 1994; 71: 753-760
        • Pickering T.G.
        Pathophysiology of exercise hypertension.
        Herz. 1987; 12: 119-124
        • Piepoli M.
        • Clark A.L.
        • Volterrani M.
        • Adamopoulos S.
        • Sleight P.
        • Coats A.J.
        Contribution of muscle afferents to the hemodynamic, autonomic, and ventilatory responses to exercise in patients with chronic heart failure: effects of physical training.
        Circulation. 1996; 93: 940-952
        • Piepoli M.
        • Ponikowski P.
        • Clark A.L.
        • Banasiak W.
        • Capucci A.
        • Coats A.J.
        A neural link to explain the “muscle hypothesis” of exercise intolerance in chronic heart failure.
        Am. Heart J. 1999; 137: 1050-1056
        • Piepoli M.F.
        • Kaczmarek A.
        • Francis D.P.
        • Davies L.C.
        • Rauchhaus M.
        • Jankowska E.A.
        • Anker S.D.
        • Capucci A.
        • Banasiak W.
        • Ponikowski P.
        Reduced peripheral skeletal muscle mass and abnormal reflex physiology in chronic heart failure.
        Circulation. 2006; 114: 126-134
        • Piepoli M.F.
        • Dimopoulos K.
        • Concu A.
        • Crisafulli A.
        Cardiovascular and ventilatory control during exercise in chronic heart failure: role of muscle reflexes.
        Int. J. Cardiol. 2008; 130: 3-10
        • Pinto T.E.
        • Gusso S.
        • Hofman P.L.
        • Derraik J.G.
        • Hornung T.S.
        • Cutfield W.S.
        • Baldi J.C.
        Systolic and diastolic abnormalities reduce the cardiac response to exercise in adolescents with type 2 diabetes.
        Diabetes Care. 2014; 37: 1439-1446
        • Pitcher G.M.
        • Henry J.L.
        Cellular mechanisms of hyperalgesia and spontaneous pain in a spinalized rat model of peripheral neuropathy: changes in myelinated afferent inputs implicated.
        Eur. J. Neurosci. 2000; 12: 2006-2020
        • Ponikowski P.P.
        • Chua T.P.
        • Francis D.P.
        • Capucci A.
        • Coats A.J.
        • Piepoli M.F.
        Muscle ergoreceptor overactivity reflects deterioration in clinical status and cardiorespiratory reflex control in chronic heart failure.
        Circulation. 2001; 104: 2324-2330
        • Pontieri V.
        • Venezuela M.K.
        • Scavone C.
        • Michelini L.C.
        Role of endogenous nitric oxide in the nucleus tratus solitarii on baroreflex control of heart rate in spontaneously hypertensive rats.
        J. Hypertens. 1998; 16: 1993-1999
        • Pop-Busui R.
        • Kirkwood I.
        • Schmid H.
        • Marinescu V.
        • Schroeder J.
        • Larkin D.
        • Yamada E.
        • Raffel D.M.
        • Stevens M.J.
        Sympathetic dysfunction in type 1 diabetes: association with impaired myocardial blood flow reserve and diastolic dysfunction.
        J. Am. Coll. Cardiol. 2004; 44: 2368-2374
        • Pop-Busui R.
        • Boulton A.J.
        • Feldman E.L.
        • Bril V.
        • Freeman R.
        • Malik R.A.
        • Sosenko J.M.
        • Ziegler D.
        Diabetic neuropathy: a position statement by the American Diabetes Association.
        Diabetes Care. 2017; 40: 136-154
        • Potts J.T.
        Exercise and sensory integration. Role of the nucleus tractus solitarius.
        Ann. N. Y. Acad. Sci. 2001; 940: 221-236
        • Prevention C.f.D.C.a
        Diabetes Report Card 2017.
        Centers for Disease Control and Prevention, US Dept of Health and Human Services, 2018
        • Price A.
        • Raheja P.
        • Wang Z.
        • Arbique D.
        • Adams-Huet B.
        • Mitchell J.H.
        • Victor R.G.
        • Thomas G.D.
        • Vongpatanasin W.
        Differential effects of nebivolol versus metoprolol on functional sympatholysis in hypertensive humans.
        Hypertension. 2013; 61: 1263-1269
        • Ratchford S.M.
        • Broxterman R.M.
        • La Salle D.T.
        • Kwon O.S.
        • Park S.Y.
        • Hopkins P.N.
        • Richardson R.S.
        • Trinity J.D.
        Salt restriction lowers blood pressure at rest and during exercise without altering peripheral hemodynamics in hypertensive individuals.
        Am. J. Physiol. Heart Circ. Physiol. 2019; 317: H1194-H1202
        • Regensteiner J.G.
        • Bauer T.A.
        • Reusch J.E.
        • Quaife R.A.
        • Chen M.Y.
        • Smith S.C.
        • Miller T.M.
        • Groves B.M.
        • Wolfel E.E.
        Cardiac dysfunction during exercise in uncomplicated type 2 diabetes.
        Med. Sci. Sports Exerc. 2009; 41: 977-984
        • Reynolds L.J.
        • Credeur D.P.
        • Manrique C.
        • Padilla J.
        • Fadel P.J.
        • Thyfault J.P.
        Obesity, type 2 diabetes, and impaired insulin-stimulated blood flow: role of skeletal muscle NO synthase and endothelin-1.
        J. Appl. Physiol. 2017; 122: 38-47
        • Roberto S.
        • Marongiu E.
        • Pinna M.
        • Angius L.
        • Olla S.
        • Bassareo P.
        • Tocco F.
        • Concu A.
        • Milia R.
        • Crisafulli A.
        Altered hemodynamics during muscle metaboreflex in young type 1 diabetes patients.
        J. Appl. Physiol. 2012; 113: 1323-1331
        • Roberto S.
        • Mulliri G.
        • Milia R.
        • Solinas R.
        • Pinna V.
        • Sainas G.
        • Piepoli M.F.
        • Crisafulli A.
        Hemodynamic response to muscle reflex is abnormal in patients with heart failure with preserved ejection fraction.
        J. Appl. Physiol. 2017; 122: 376-385
        • Rondon M.U.
        • Laterza M.C.
        • de Matos L.D.
        • Trombetta I.C.
        • Braga A.M.
        • Roveda F.
        • Alves M.J.
        • Krieger E.M.
        • Negrao C.E.
        Abnormal muscle metaboreflex control of sympathetic activity in never-treated hypertensive subjects.
        Am. J. Hypertens. 2006; 19: 951-957
        • Rotto D.M.
        • Kaufman M.P.
        Effect of metabolic products of muscular contraction on discharge of group III and IV afferents.
        J. Appl. Physiol. 1988; 64: 2306-2313
        • Rotto D.M.
        • Stebbins C.L.
        • Kaufman M.P.
        Reflex cardiovascular and ventilatory responses to increasing H+ activity in cat hindlimb muscle.
        J. Appl. Physiol. 1989; 67: 256-263
        • Rotto D.M.
        • Schultz H.D.
        • Longhurst J.C.
        • Kaufman M.P.
        Sensitization of group III muscle afferents to static contraction by arachidonic acid.
        J. Appl. Physiol. 1990; 68: 861-867
        • Rowell L.B.
        • O’Leary D.S.
        Reflex control of the circulation during exercise: chemoreflexes and mechanoreflexes.
        J. Appl. Physiol. 1990; 69: 407-418
        • Rybicki K.J.
        • Waldrop T.G.
        • Kaufman M.P.
        Increasing gracilis muscle interstitial potassium concentrations stimulate group III and IV afferents.
        J. Appl. Physiol. 1985; 58: 936-941
        • Sabino-Carvalho J.L.
        • Teixeira A.L.
        • Samora M.
        • Daher M.
        • Vianna L.C.
        Blunted cardiovascular responses to exercise in Parkinson’s disease patients: role of the muscle metaboreflex.
        J. Neurophysiol. 2018; 120: 1516-1524
        • Sander M.
        • Macefield V.G.
        • Henderson L.A.
        Cortical and brain stem changes in neural activity during static handgrip and postexercise ischemia in humans.
        J. Appl. Physiol. 2010; 108: 1691-1700
        • Sanderson B.C.
        • Rollins K.S.
        • Hopkins T.D.
        • Butenas A.L.
        • Felice K.P.
        • Ade C.J.
        • Copp S.W.
        GsMTx4 reduces the reflex pressor response during dynamic hindlimb skeletal muscle stretch in decerebrate rats.
        Physiol Rep. 2019; 7e13974
        • Sausen M.T.
        • Delaney E.P.
        • Stillabower M.E.
        • Farquhar W.B.
        Enhanced metaboreflex sensitivity in hypertensive humans.
        Eur. J. Appl. Physiol. 2009; 105: 351-356
        • Schobel H.P.
        • Heusser K.
        • Schmieder R.E.
        • Veelken R.
        • Fischer T.
        • Luft F.C.
        Evidence against elevated sympathetic vasoconstrictor activity in borderline hypertension.
        J. Am. Soc. Nephrol. 1998; 9: 1581-1587
        • Scott A.C.
        • Francis D.P.
        • Davies L.C.
        • Ponikowski P.
        • Coats A.J.
        • Piepoli M.F.
        Contribution of skeletal muscle ‘ergoreceptors’ in the human leg to respiratory control in chronic heart failure.
        J. Physiol. 2000; 529: 863-870
        • Scott J.A.
        • Coombes J.S.
        • Prins J.B.
        • Leano R.L.
        • Marwick T.H.
        • Sharman J.E.
        Patients with type 2 diabetes have exaggerated brachial and central exercise blood pressure: relation to left ventricular relative wall thickness.
        Am. J. Hypertens. 2008; 21: 715-721
        • Sheriff D.D.
        • O’Leary D.S.
        • Scher A.M.
        • Rowell L.B.
        Baroreflex attenuates pressor response to graded muscle ischemia in exercising dogs.
        Am. J. Phys. 1990; 258: H305-H310
        • Sheriff D.D.
        • Rowell L.B.
        • Scher A.M.
        Is rapid rise in vascular conductance at onset of dynamic exercise due to muscle pump?.
        Am. J. Phys. 1993; 265: H1227-H1234
        • Shoemaker J.K.
        • Naylor H.L.
        • Hogeman C.S.
        • Sinoway L.I.
        Blood flow dynamics in heart failure.
        Circulation. 1999; 99: 3002-3008
        • Sidhu S.K.
        • Weavil J.C.
        • Rossman M.J.
        • Jessop J.E.
        • Bledsoe A.D.
        • Buys M.J.
        • Supiano M.S.
        • Richardson R.S.
        • Amann M.
        Exercise pressor reflex contributes to the cardiovascular abnormalities characterizing: hypertensive humans during exercise.
        Hypertension. 2019; 74: 1468-1475
        • Silber D.H.
        • Sutliff G.
        • Yang Q.X.
        • Smith M.B.
        • Sinoway L.I.
        • Leuenberger U.A.
        Altered mechanisms of sympathetic activation during rhythmic forearm exercise in heart failure.
        J. Appl. Physiol. 1998; 84: 1551-1559
        • Simmonds S.S.
        • Lay J.
        • Stocker S.D.
        Dietary salt intake exaggerates sympathetic reflexes and increases blood pressure variability in normotensive rats.
        Hypertension. 2014; 64: 583-589
        • Smith S.A.
        • Mitchell J.H.
        • Li J.
        Independent modification of baroreceptor and exercise pressor reflex function by nitric oxide in nucleus tractus solitarius.
        Am. J. Physiol. Heart Circ. Physiol. 2005; 288: H2068-H2076
        • Smith S.A.
        • Mitchell J.H.
        • Naseem R.H.
        • Garry M.G.
        Mechanoreflex mediates the exaggerated exercise pressor reflex in heart failure.
        Circulation. 2005; 112: 2293-2300
        • Smith S.A.
        • Williams M.A.
        • Mitchell J.H.
        • Mammen P.P.
        • Garry M.G.
        The capsaicin-sensitive afferent neuron in skeletal muscle is abnormal in heart failure.
        Circulation. 2005; 111: 2056-2065
        • Smith S.A.
        • Williams M.A.
        • Leal A.K.
        • Mitchell J.H.
        • Garry M.G.
        Exercise pressor reflex function is altered in spontaneously hypertensive rats.
        J. Physiol. 2006; 577: 1009-1020
        • Smith S.A.
        • Leal A.K.
        • Williams M.A.
        • Murphy M.N.
        • Mitchell J.H.
        • Garry M.G.
        The TRPv1 receptor is a mediator of the exercise pressor reflex in rats.
        J. Physiol. 2010; 588: 1179-1189
        • Smith S.A.
        • Leal A.K.
        • Murphy M.N.
        • Downey R.M.
        • Mizuno M.
        Muscle mechanoreflex overactivity in hypertension: a role for centrally-derived nitric oxide.
        Autonomic Neuroscience: Basic & Clinical. 2015; 188: 58-63
        • Song S.H.
        Early-onset type 2 diabetes: high lifetime risk for cardiovascular disease.
        Lancet Diabetes Endocrinol. 2016; 4: 87-88
        • Spranger M.D.
        • Kaur J.
        • Sala-Mercado J.A.
        • Krishnan A.C.
        • Abu-Hamdah R.
        • Alvarez A.
        • Machado T.M.
        • Augustyniak R.A.
        • O’Leary D.S.
        Exaggerated coronary vasoconstriction limits muscle metaboreflex-induced increases in ventricular performance in hypertension.
        Am. J. Physiol. Heart Circ. Physiol. 2017; 312: H68-H79
        • Stepp D.W.
        • Frisbee J.C.
        Augmented adrenergic vasoconstriction in hypertensive diabetic obese Zucker rats.
        Am. J. Physiol. Heart Circ. Physiol. 2002; 282: H816-H820
        • Sterns D.A.
        • Ettinger S.M.
        • Gray K.S.
        • Whisler S.K.
        • Mosher T.J.
        • Smith M.B.
        • Sinoway L.I.
        Skeletal muscle metaboreceptor exercise responses are attenuated in heart failure.
        Circulation. 1991; 84: 2034-2039
        • Stone A.J.
        • Copp S.W.
        • Kim J.S.
        • Kaufman M.P.
        Combined, but not individual, blockade of ASIC3, P2X, and EP4 receptors attenuates the exercise pressor reflex in rats with freely perfused hindlimb muscles.
        J. Appl. Physiol. 2015; 119: 1330-1336
        • Sun W.
        • Miao B.
        • Wang X.C.
        • Duan J.H.
        • Wang W.T.
        • Kuang F.
        • Xie R.G.
        • Xing J.L.
        • Xu H.
        • Song X.J.
        • Luo C.
        • Hu S.J.
        Reduced conduction failure of the main axon of polymodal nociceptive C-fibres contributes to painful diabetic neuropathy in rats.
        Brain: A Journal of Neurology. 2012; 135: 359-375
        • Szczot M.
        • Liljencrantz J.
        • Ghitani N.
        • Barik A.
        • Lam R.
        • Thompson J.H.
        • Bharucha-Goebel D.
        • Saade D.
        • Necaise A.
        • Donkervoort S.
        • Foley A.R.
        • Gordon T.
        • Case L.
        • Bushnell M.C.
        • Bonnemann C.G.
        • Chesler A.T.
        PIEZO2 mediates injury-induced tactile pain in mice and humans.
        Sci. Transl. Med. 2018; 10: eaat9892
        • Tai M.H.
        • Hsiao M.
        • Chan J.Y.
        • Lo W.C.
        • Wang F.S.
        • Liu G.S.
        • Howng S.L.
        • Tseng C.J.
        Gene delivery of endothelial nitric oxide synthase into nucleus tractus solitarii induces biphasic response in cardiovascular functions of hypertensive rats.
        Am. J. Hypertens. 2004; 17: 63-70
        • Tallarida G.
        • Baldoni F.
        • Peruzzi G.
        • Brindisi F.
        • Raimondi G.
        • Sangiorgi M.
        Cardiovascular and respiratory chemoreflexes from the hindlimb sensory receptors evoked by intra-arterial injection of bradykinin and other chemical agents in the rabbit.
        J. Pharmacol. Exp. Ther. 1979; 208: 319-329
        • Taylor C.E.
        • Boulton D.
        • Howden E.J.
        • Siebenmann C.
        • Macefield V.G.
        Central command increases muscle sympathetic nerve activity more to contracting than noncontracting muscle during rhythmic isotonic leg exercise.
        J. Neurophysiol. 2019; 121: 1704-1710
        • Thaning P.
        • Bune L.T.
        • Zaar M.
        • Saltin B.
        • Rosenmeier J.B.
        Functional sympatholysis during exercise in patients with type 2 diabetes with intact response to acetylcholine.
        Diabetes Care. 2011; 34: 1186-1191
        • Thomas J.A.
        • Marks B.H.
        Plasma norepinephrine in congestive heart failure.
        Am. J. Cardiol. 1978; 41: 233-243
        • Tominaga M.
        • Tominaga T.
        Structure and function of TRPV1.
        Pflugers Arch. 2005; 451: 143-150
        • Tsuchimochi H.
        • McCord J.L.
        • Hayes S.G.
        • Koba S.
        • Kaufman M.P.
        Chronic femoral artery occlusion augments exercise pressor reflex in decerebrated rats.
        Am. J. Physiol. Heart Circ. Physiol. 2010; 299: H106-H113
        • Vanhees L.
        • Fagard R.
        • Thijs L.
        • Staessen J.
        • Amery A.
        Prognostic significance of peak exercise capacity in patients with coronary artery disease.
        J. Am. Coll. Cardiol. 1994; 23: 358-363
        • Vanhoutte P.M.
        Adjustments in the peripheral circulation in chronic heart failure.
        Eur. Heart J. 1983; 4: 67-83
        • Vianna L.C.
        • Fisher J.P.
        Reflex control of the cardiovascular system during exercise in disease.
        Current Opinion in Physiology. 2019; 10: 110-117
        • Victor R.G.
        • Seals D.R.
        • Mark A.L.
        Differential control of heart rate and sympathetic nerve activity during dynamic exercise. Insight from intraneural recordings in humans.
        J. Clin. Invest. 1987; 79: 508-516
        • Victor R.G.
        • Pryor S.L.
        • Secher N.H.
        • Mitchell J.H.
        Effects of partial neuromuscular blockade on sympathetic nerve responses to static exercise in humans.
        Circ. Res. 1989; 65: 468-476
        • Victor R.G.
        • Rotto D.M.
        • Pryor S.L.
        • Kaufman M.P.
        Stimulation of renal sympathetic activity by static contraction: evidence for mechanoreceptor-induced reflexes from skeletal muscle.
        Circ. Res. 1989; 64: 592-599
        • Victor R.G.
        • Secher N.H.
        • Lyson T.
        • Mitchell J.H.
        Central command increases muscle sympathetic nerve activity during intense intermittent isometric exercise in humans.
        Circ. Res. 1995; 76: 127-131
        • Vongpatanasin W.
        • Wang Z.
        • Arbique D.
        • Arbique G.
        • Adams-Huet B.
        • Mitchell J.H.
        • Victor R.G.
        • Thomas G.D.
        Functional sympatholysis is impaired in hypertensive humans.
        J. Physiol. 2011; 589: 1209-1220
        • Wallin B.G.
        • Burke D.
        • Gandevia S.C.
        Coherence between the sympathetic drives to relaxed and contracting muscles of different limbs of human subjects.
        J. Physiol. 1992; 455: 219-233
        • Wang H.J.
        • Pan Y.X.
        • Wang W.Z.
        • Zucker I.H.
        • Wang W.
        NADPH oxidase-derived reactive oxygen species in skeletal muscle modulates the exercise pressor reflex.
        J. Appl. Physiol. 2009; 107: 450-459
        • Wang H.J.
        • Li Y.L.
        • Gao L.
        • Zucker I.H.
        • Wang W.
        Alteration in skeletal muscle afferents in rats with chronic heart failure.
        J. Physiol. 2010; 588: 5033-5047
        • Whelton P.K.
        • Carey R.M.
        • Aronow W.S.
        • Casey Jr., D.E.
        • Collins K.J.
        • Dennison Himmelfarb C.
        • DePalma S.M.
        • Gidding S.
        • Jamerson K.A.
        • Jones D.W.
        • MacLaughlin E.J.
        • Muntner P.
        • Ovbiagele B.
        • Smith Jr., S.C.
        • Spencer C.C.
        • Stafford R.S.
        • Taler S.J.
        • Thomas R.J.
        • Williams Sr., K.A.
        • Williamson J.D.
        • Wright Jr., J.T.
        2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines.
        Hypertension. 2018; 71: e13-e115
        • Wild S.
        • Roglic G.
        • Green A.
        • Sicree R.
        • King H.
        Global prevalence of diabetes: estimates for the year 2000 and projections for 2030.
        Diabetes Care. 2004; 27: 1047-1053
        • Williamson J.W.
        • McColl R.
        • Mathews D.
        • Mitchell J.H.
        • Raven P.B.
        • Morgan W.P.
        Hypnotic manipulation of effort sense during dynamic exercise: cardiovascular responses and brain activation.
        J. Appl. Physiol. 2001; 90: 1392-1399
        • Williamson J.W.
        • Fadel P.J.
        • Mitchell J.H.
        New insights into central cardiovascular control during exercise in humans: a central command update.
        Exp. Physiol. 2006; 91: 51-58
        • Wu W.C.
        • Wang Y.
        • Kao L.S.
        • Tang F.I.
        • Chai C.Y.
        Nitric oxide reduces blood pressure in the nucleus tractus solitarius: a real time electrochemical study.
        Brain Res. Bull. 2002; 57: 171-177
        • Xu Z.Z.
        • Kim Y.H.
        • Bang S.
        • Zhang Y.
        • Berta T.
        • Wang F.
        • Oh S.B.
        • Ji R.R.
        Inhibition of mechanical allodynia in neuropathic pain by TLR5-mediated A-fiber blockade.
        Nat. Med. 2015; 21: 1326-1331
        • Yamauchi K.
        • Tsuchimochi H.
        • Stone A.J.
        • Stocker S.D.
        • Kaufman M.P.
        Increased dietary salt intake enhances the exercise pressor reflex.
        Am. J. Physiol. Heart Circ. Physiol. 2014; 306: H450-H454
        • Zhao W.
        • Swanson S.A.
        • Ye J.
        • Li X.
        • Shelton J.M.
        • Zhang W.
        • Thomas G.D.
        Reactive oxygen species impair sympathetic vasoregulation in skeletal muscle in angiotensin II-dependent hypertension.
        Hypertension. 2006; 48: 637-643
        • Zhu J.
        • Huang T.
        • Lombard J.H.
        Effect of high-salt diet on vascular relaxation and oxidative stress in mesenteric resistance arteries.
        J. Vasc. Res. 2007; 44: 382-390
        • Zimmerman M.C.
        • Lazartigues E.
        • Sharma R.V.
        • Davisson R.L.
        Hypertension caused by angiotensin II infusion involves increased superoxide production in the central nervous system.
        Circ. Res. 2004; 95: 210-216
        • Zorena K.
        • Mysliwska J.
        • Mysliwiec M.
        • Rybarczyk-Kapturska K.
        • Malinowska E.
        • Wisniewski P.
        • Raczynska K.
        Association between vascular endothelial growth factor and hypertension in children and adolescents type I diabetes mellitus.
        J. Hum. Hypertens. 2010; 24: 755-762
        • Zucker I.H.
        • Schultz H.D.
        • Patel K.P.
        • Wang H.
        Modulation of angiotensin II signaling following exercise training in heart failure.
        Am. J. Physiol. Heart Circ. Physiol. 2015; 308: H781-H791