Advertisement

Relationship between heart rate variability and endothelial function in healthy subjects

      Abstract

      In various diseased states reduced cardiac vagal activity is accompanied by impaired endothelial function. Evidence from animal studies indicates interaction between the two systems, but such data from human studies is limited. The aim of this study was to test the hypothesis that cardiac vagal activity and endothelial function are related in healthy individuals.
      46 young males were studied. From 10 minute long ECG recordings mean RR-interval and time and frequency domain vagal heart rate variability indices (RMSSD; pNN50 and HF, respectively) were determined. Heart rate variability indices were used to define cardiac vagal activity. Endothelial function was assessed by measuring brachial artery flow mediated dilation. Hyperemic, diastolic shear rate was used to normalize flow mediated dilation.
      All three vagal heart rate variability indices correlated significantly and positively with flow mediated dilation across subjects, with r values within the range of 0.43–0.52, p<0.01 for all relations. After adjusting for potential confounders, vagal heart rate variability indices remained significantly associated with normalized flow mediated dilation. RR-interval was related to most heart rate variability indices, but was not related to flow mediated dilation.
      Our data demonstrate that vagal heart rate variability indices are related to flow mediated dilation across healthy male subjects. The results cannot serve as evidence of a causal relationship, but are of interest and render for further investigation into underlying mechanisms.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Autonomic Neuroscience: Basic and Clinical
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Anderson T.J.
        • Uehata A.
        • Gerhard M.D.
        • Meredith I.T.
        • Knab S.
        • Delagrange D.
        • Lieberman E.H.
        • Ganz P.
        • Creager M.A.
        • Yeung A.C.
        • et al.
        Close relation of endothelial function in the human coronary and peripheral circulations.
        J. Am. Coll. Cardiol. 1995; 26: 1235-1241
        • Bonyhay I.
        • Jokkel G.
        • Kollai M.
        Relation between baroreflex sensitivity and carotid artery elasticity in healthy humans.
        Am. J. Physiol. 1996; 271: H1139-H1144
        • Burke J.H.
        • Goldberger J.J.
        • Ehlert F.A.
        • Kruse J.T.
        • Parker M.A.
        • Kadish A.H.
        Gender differences in heart rate before and after autonomic blockade: evidence against an intrinsic gender effect.
        Am. J. Med. 1996; 100: 537-543
        • Burnstock G.
        • Ralevic V.
        New insights into the local regulation of blood flow by perivascular nerves and endothelium.
        Br. J. Plast. Surg. 1994; 47: 527-543
        • Carlson S.H.
        • Wyss J.M.
        Neurohormonal regulation of the sympathetic nervous system: new insights into central mechanisms of action.
        Curr. Hypertens. Rep. 2008; 10: 233-240
        • Chowdhary S.
        • Townend J.N.
        Nitric oxide and hypertension: not just an endothelium derived relaxing factor!.
        J. Hum. Hypertens. 2001; 15: 219-227
        • Chowdhary S.
        • Vaile J.C.
        • Fletcher J.
        • Ross H.F.
        • Coote J.H.
        • Townend J.N.
        Nitric oxide and cardiac autonomic control in humans.
        Hypertension. 2000; 36: 264-269
        • Conlon K.
        • Collins T.
        • Kidd C.
        The role of nitric oxide in the control by the vagal nerves of the heart of the ferret.
        Exp. Physiol. 1998; 83: 469-480
        • Debbabi H.
        • Bonnin P.
        • Ducluzeau P.H.
        • Leftheriotis G.
        • Levy B.I.
        Noninvasive assessment of endothelial function in the skin microcirculation.
        Am. J. Hypertens. 2010; 23: 541-546
        • Eckberg D.L.
        The human respiratory gate.
        J. Physiol. 2003; 548: 339-352
        • Gerhard M.
        • Roddy M.A.
        • Creager S.J.
        • Creager M.A.
        Aging progressively impairs endothelium-dependent vasodilation in forearm resistance vessels of humans.
        Hypertension. 1996; 27: 849-853
        • Ghiadoni L.
        • Faita F.
        • Salvetti M.
        • Cordiano C.
        • Biggi A.
        • Puato M.
        • Di Monaco A.
        • De Siati L.
        • Volpe M.
        • Ambrosio G.
        • et al.
        Assessment of flow mediated dilation reproducibility: a nationwide multicenter study.
        J. Hypertens. 2012; 30: 1399-1405
        • Goldberger J.J.
        • Challapalli S.
        • Tung R.
        • Parker M.A.
        • Kadish A.H.
        Relationship of heart rate variability to parasympathetic effect.
        Circulation. 2001; 103: 1977-1983
        • Gori T.
        • Di Stolfo G.
        • Sicuro S.
        • Dragoni S.
        • Lisi M.
        • Parker J.D.
        • Forconi S.
        Correlation analysis between different parameters of conduit artery and microvascular vasodilation.
        Clin. Hemorheol. Microcirc. 2006; 35: 509-515
        • Hagg U.
        • Wandt B.
        • Bergstrom G.
        • Volkmann R.
        • Gan L.M.
        Physical exercise capacity is associated with coronary and peripheral vascular function in healthy young adults.
        Am. J. Physiol. Heart Circ. Physiol. 2005; 289: H1627-H1634
        • Hamburg N.M.
        • Palmisano J.
        • Larson M.G.
        • Sullivan L.M.
        • Lehman B.T.
        • Vasan R.S.
        • Levy D.
        • Mitchell G.F.
        • Vita J.A.
        • Benjamin E.J.
        Relation of brachial and digital measures of vascular function in the community: the Framingham heart study.
        Hypertension. 2011; 57: 390-396
        • Hashimoto M.
        • Akishita M.
        • Eto M.
        • Ishikawa M.
        • Kozaki K.
        • Toba K.
        • Sagara Y.
        • Taketani Y.
        • Orimo H.
        • Ouchi Y.
        Modulation of endothelium-dependent flow-mediated dilatation of the brachial artery by sex and menstrual cycle.
        Circulation. 1995; 92: 3431-3435
        • Hedblad B.
        • Wikstrand J.
        • Janzon L.
        • Wedel H.
        • Berglund G.
        Low-dose metoprolol CR/XL and fluvastatin slow progression of carotid intima-media thickness: main results from the Beta-Blocker Cholesterol-Lowering Asymptomatic Plaque Study (BCAPS).
        Circulation. 2001; 103: 1721-1726
        • Hijmering M.L.
        • Stroes E.S.
        • Olijhoek J.
        • Hutten B.A.
        • Blankestijn P.J.
        • Rabelink T.J.
        Sympathetic activation markedly reduces endothelium-dependent, flow-mediated vasodilation.
        J. Am. Coll. Cardiol. 2002; 39: 683-688
        • Hull Jr., S.S.
        • Vanoli E.
        • Adamson P.B.
        • De Ferrari G.M.
        • Foreman R.D.
        • Schwartz P.J.
        Do increases in markers of vagal activity imply protection from sudden death? The case of scopolamine.
        Circulation. 1995; 91: 2516-2519
        • Juonala M.
        • Kahonen M.
        • Laitinen T.
        • Hutri-Kahonen N.
        • Jokinen E.
        • Taittonen L.
        • Pietikainen M.
        • Helenius H.
        • Viikari J.S.
        • Raitakari O.T.
        Effect of age and sex on carotid intima-media thickness, elasticity and brachial endothelial function in healthy adults: the cardiovascular risk in Young Finns Study.
        Eur. Heart J. 2008; 29: 1198-1206
        • Kollai M.
        • Jokkel G.
        • Bonyhay I.
        • Tomcsanyi J.
        • Naszlady A.
        Relation between baroreflex sensitivity and cardiac vagal tone in humans.
        Am. J. Physiol. 1994; 266: H21-H27
        • Koskinen T.
        • Kahonen M.
        • Jula A.
        • Laitinen T.
        • Keltikangas-Jarvinen L.
        • Viikari J.
        • Valimaki I.
        • Raitakari O.T.
        Short-term heart rate variability in healthy young adults: the Cardiovascular Risk in Young Finns Study.
        Auton. Neurosci. 2009; 145: 81-88
        • Malik M.
        • Bigger J.T.
        • Camm A.J.
        • Kleiger R.E.
        • Malliani A.
        • Moss A.J.
        • Schwartz P.J.
        Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology.
        Eur. Heart J. 1996; 17: 354-381
        • Mceniery C.M.
        • Wallace S.
        • Mackenzie I.S.
        • Mcdonnell B.
        • Yasmin
        • Newby D.E.
        • Cockcroft J.R.
        • Wilkinson I.B.
        Endothelial function is associated with pulse pressure, pulse wave velocity, and augmentation index in healthy humans.
        Hypertension. 2006; 48: 602-608
        • Mitchell G.F.
        • Parise H.
        • Vita J.A.
        • Larson M.G.
        • Warner E.
        • Keaney Jr., J.F.
        • Keyes M.J.
        • Levy D.
        • Vasan R.S.
        • Benjamin E.J.
        Local shear stress and brachial artery flow-mediated dilation: the Framingham Heart Study.
        Hypertension. 2004; 44: 134-139
        • Otto M.E.
        • Svatikova A.
        • Barretto R.B.
        • Santos S.
        • Hoffmann M.
        • Khandheria B.
        • Somers V.
        Early morning attenuation of endothelial function in healthy humans.
        Circulation. 2004; 109: 2507-2510
        • Parati G.
        • Bilo G.
        • Vettorello M.
        • Groppelli A.
        • Maronati A.
        • Tortorici E.
        • Caldara G.
        • Mancia G.
        Assessment of overall blood pressure variability and its different components.
        Blood Press. Monit. 2003; 8: 155-159
        • Park J.B.
        • Charbonneau F.
        • Schiffrin E.L.
        Correlation of endothelial function in large and small arteries in human essential hypertension.
        J. Hypertens. 2001; 19: 415-420
        • Pawlik G.
        • Rackl A.
        • Bing R.J.
        Quantitative capillary topography and blood flow in the cerebral cortex of cats: an in vivo microscopic study.
        Brain Res. 1981; 208: 35-58
        • Pitzalis M.V.
        • Mastropasqua F.
        • Massari F.
        • Passantino A.
        • Totaro P.
        • Forleo C.
        • Rizzon P.
        Beta-blocker effects on respiratory sinus arrhythmia and baroreflex gain in normal subjects.
        Chest. 1998; 114: 185-191
        • Ross R.
        The pathogenesis of atherosclerosis: a perspective for the 1990s.
        Nature. 1993; 362: 801-809
        • Sakuma I.
        • Togashi H.
        • Yoshioka M.
        • Saito H.
        • Yanagida M.
        • Tamura M.
        • Kobayashi T.
        • Yasuda H.
        • Gross S.S.
        • Levi R.
        NG-methyl-L-arginine, an inhibitor of L-arginine-derived nitric oxide synthesis, stimulates renal sympathetic nerve activity in vivo. A role for nitric oxide in the central regulation of sympathetic tone?.
        Circ. Res. 1992; 70: 607-611
        • Seals D.R.
        • Chase P.B.
        Influence of physical training on heart rate variability and baroreflex circulatory control.
        J. Appl. Physiol. 1989; 66: 1886-1895
        • Spieker L.E.
        • Corti R.
        • Binggeli C.
        • Luscher T.F.
        • Noll G.
        Baroreceptor dysfunction induced by nitric oxide synthase inhibition in humans.
        J. Am. Coll. Cardiol. 2000; 36: 213-218
        • Sverrisdottir Y.B.
        • Jansson L.M.
        • Hagg U.
        • Gan L.M.
        Muscle sympathetic nerve activity is related to a surrogate marker of endothelial function in healthy individuals.
        PLoS One. 2010; 5: e9257
        • Tarkiainen T.H.
        • Timonen K.L.
        • Tiittanen P.
        • Hartikainen J.E.
        • Pekkanen J.
        • Hoek G.
        • Ibald-Mulli A.
        • Vanninen E.J.
        Stability over time of short-term heart rate variability.
        Clin. Auton. Res. 2005; 15: 394-399
        • Thijssen D.H.
        • Black M.A.
        • Pyke K.E.
        • Padilla J.
        • Atkinson G.
        • Harris R.A.
        • Parker B.
        • Widlansky M.E.
        • Tschakovsky M.E.
        • Green D.J.
        Assessment of flow-mediated dilation in humans: a methodological and physiological guideline.
        Am. J. Physiol. Heart Circ. Physiol. 2011; 300: H2-H12
        • Travagli R.A.
        • Gillis R.A.
        Nitric oxide-mediated excitatory effect on neurons of dorsal motor nucleus of vagus.
        Am. J. Physiol. 1994; 266: G154-G160
        • Tsuji H.
        • Venditti Jr., F.J.
        • Manders E.S.
        • Evans J.C.
        • Larson M.G.
        • Feldman C.L.
        • Levy D.
        Determinants of heart rate variability.
        J. Am. Coll. Cardiol. 1996; 28: 1539-1546
        • Vanhoutte P.M.
        The endothelium—modulator of vascular smooth-muscle tone.
        N. Engl. J. Med. 1988; 319: 512-513
        • Yamasaki Y.
        • Kodama M.
        • Matsuhisa M.
        • Kishimoto M.
        • Ozaki H.
        • Tani A.
        • Ueda N.
        • Ishida Y.
        • Kamada T.
        Diurnal heart rate variability in healthy subjects: effects of aging and sex difference.
        Am. J. Physiol. 1996; 271: H303-H310
        • Young C.N.
        • Fisher J.P.
        • Gallagher K.M.
        • Whaley-Connell A.
        • Chaudhary K.
        • Victor R.G.
        • Thomas G.D.
        • Fadel P.J.
        Inhibition of nitric oxide synthase evokes central sympatho-excitation in healthy humans.
        J. Physiol. 2009; 587: 4977-4986