Abstract
Cardiac sympathetic neurons stimulate heart rate and the force of contraction through
release of norepinephrine. Nerve growth factor modulates sympathetic transmission
through activation of TrkA and p75NTR. Nerve growth factor plays an important role
in post-infarct sympathetic remodeling. We used mice lacking p75NTR to examine the
effect of altered nerve growth factor signaling on sympathetic neuropeptide expression,
cardiac norepinephrine, and ventricular function after myocardial infarction. Infarct
size was similar in wildtype and p75NTR−/− mice after ischemia–reperfusion surgery.
Likewise, mRNAs encoding vasoactive intestinal peptide, galanin, and pituitary adenylate
cyclase activating peptides were identical in wildtype and p75NTR−/− cardiac sympathetic
neurons, as was expression of the TrkA neurotrophin receptor. Norepinephrine content
was elevated in the base of the p75NTR−/− ventricle compared to wildtype, but levels
were identical below the site of occlusion. Left ventricular pressure, dP/dtMAX, and dP/dtMIN were measured under isoflurane anesthesia 3 and 7 days after surgery. Ventricular pressure decreased significantly 3 days after infarction, and deficits in dP/dtMAX were revealed by stimulating beta receptors with dobutamine and release of endogenous
norepinephrine with tyramine. dP/dtMIN was not altered by genotype or surgical group. Few differences were observed between
genotypes 3 days after surgery, in contrast to low pressure and dP/dtMAX previously reported in control p75NTR−/− animals. Seven days after surgery ventricular
pressure and dP/dtMAX were significantly lower in p75NTR−/− hearts compared to WT hearts. Thus, the lack
of p75NTR did not enhance cardiac function after myocardial infarction.
Keywords
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References
- Protective role of nerve growth factor against postischemic dysfunction of sympathetic coronary innervation.Circulation. 1997; 95: 213-220
- Cardiac Ischemia–Reperfusion Regulates Sympathetic Neuropeptide Expression Through gp130-dependent and Independent Mechanisms.Neuropeptides. 2010; 45: 33-42
- The p75 neurotrophin receptor mediates neuronal apoptosis and is essential for naturally occurring sympathetic neuron death.J. Cell Biol. 1998; 140: 911-923
- Transmural myocardial infarction in the dog produces sympathectomy in noninfarcted myocardium.Circulation. 1983; 67: 787-796
- Sympathetic neuroblasts undergo a developmental switch in trophic dependence.Development. 1993; 119: 597-610
- Nerve sprouting and sudden cardiac death.Circ. Res. 2000; 86: 816-821
- Relationship between regional cardiac hyperinnervation and ventricular arrhythmia.Circulation. 2000; 101: 1960-1969
- Mice lacking nerve growth factor display perinatal loss of sensory and sympathetic neurons yet develop basal forebrain cholinergic neurons.Cell. 1994; 76: 1001-1011
- Heterogeneous sympathetic innervation in German shepherd dogs with inherited ventricular arrhythmia and sudden cardiac death.Circulation. 1997; 96: 1337-1342
- Pituitary adenylate cyclase activating polypeptide protects cardiomyocytes against oxidative stress-induced apoptosis.Peptides. 2006; 27: 87-94
- Heterogeneous requirement of NGF for sympathetic target innervation in vivo.J. Neurosci. 2004; 24: 743-751
- Time course of sympathetic neural hyperactivity after uncomplicated acute myocardial infarction.Circulation. 2002; 106: 793-797
- Regulation of cardiac innervation and function via the p75 neurotrophin receptor.Auton. Neurosci. 2008; 140: 40-48
- Myocardial infarction stimulates galanin expression in cardiac sympathetic neurons.Neuropeptides. 2005; 39: 89-95
- TrkA and mitogen-activated protein kinase phosphorylation are enhanced in sympathetic neurons lacking functional p75 neurotrophin receptor expression.Eur. J. Neurosci. 2004; 19: 2903-2908
- Sympathetic hyperinnervation and inflammatory cell NGF synthesis following myocardial infarction in rats.Brain Res. 2006; 1124: 142-154
- Nerve growth factor and brain-derived neurotrophic factor mRNAs are regulated in distinct cell populations of rat heart after ischaemia and reperfusion.J. Pathol. 2001; 194: 247-253
- Cholinergic neurons of mouse intrinsic cardiac ganglia contain noradrenergic enzymes, norepinephrine transporters, and the neurotrophin receptors tropomyosin-related kinase A and p75.Neuroscience. 2008; 156: 129-142
- Deletion of the mouse {alpha}-calcitonin gene-related peptide gene increases the vulnerability of the heart to ischemia–reperfusion injury.Am J Physiol Heart Circ Physiol. 2008; 294: H1291-H1297
- Nerve growth factor is critical for cardiac sensory innervation and rescues neuropathy in diabetic hearts.Circulation. 2006; 114: 2351-2363
- Time course of denervation of efferent sympathetic and vagal nerves after occlusion of the coronary artery in the canine heart.Circ. Res. 1988; 62: 1111-1120
- The influences of p75 neurotrophin receptor and brain-derived neurotrophic factor in the sympathetic innervation of target tissues during murine postnatal development.Auton. Neurosci. 2005; 118: 32-42
- Rapid activation of the sympathetic nervous system following coronary artery occlusion: relationship to infarct size, site, and haemodynamic impact.Cardiovasc. Res. 1979; 13: 523-531
- Functionally antagonistic interactions between the TrkA and p75 neurotrophin receptors regulate sympathetic neuron growth and target innervation.J. Neurosci. 1999; 19: 5393-5408
- A neurotrophin signaling cascade coordinates sympathetic neuron development through differential control of TrkA trafficking and retrograde signaling.Cell. 2004; 118: 243-255
- Dependence on p75 for innervation of some sympathetic targets.Science. 1994; 263: 1447-1449
- Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system.Cell. 1992; 69: 737-749
- Infarction alters both the distribution and noradrenergic properties of cardiac sympathetic neurons.Am. J. Physiol Heart Circ. Physiol. 2004; 286: H2229-H2236
- The cardioprotection of calcitonin gene-related peptide-mediated preconditioning.Eur. J. Pharmacol. 2002; 442: 173-177
- VEGF-A and Semaphorin3A: modulators of vascular sympathetic innervation.Dev. Biol. 2009; 334: 119-132
- Heterogeneous ventricular sympathetic innervation, altered beta adrenergic receptor expression, and rhythm instability in mice lacking p75 neurotrophin receptor.Am J Physiol Heart Circ Physiol. 2010; 298: H1652-H1660
- Nerve growth factor decreases potassium currents and alters repetitive firing in rat sympathetic neurons.J. Neurophysiol. 2006; 96: 946-958
- p75 and TrkA signaling regulates sympathetic neuronal firing patterns via differential modulation of voltage-gated currents.J. Neurosci. 2009; 29: 5411-5424
- Nerve growth factor-mediated induction of tyrosine hydroxylase in rat superior cervical ganglia in vitro.J. Biol. Chem. 1978; 253: 8013-8015
- The biological effects of endogenous nerve growth factor on adult sensory neurons revealed by a trkA-IgG fusion molecule.Nat. Med. 1995; 1: 774-780
- Nerve growth factor promotes cardiac repair following myocardial infarction.Circ. Res. 2010; 106: 1275-1284
- Scintigraphic and electrophysiological evidence of canine myocardial sympathetic denervation and reinnervation produced by myocardial infarction or phenol application.Circulation. 1988; 78: 1008-1019
- Spatial distribution of nerve sprouting after myocardial infarction in mice.Heart Rhythm. 2006; 3: 728-736
- The absence of gp130 in dopamine beta hydroxylase-expressing neurons leads to autonomic imbalance and increased reperfusion arrhythmias.Am J Physiol Heart Circ Physiol. 2009; 297: H960-H967
- Infarction-induced cytokines cause local depletion of tyrosine hydroxylase in cardiac sympathetic nerves.Exp. Physiol. 2009; 95: 304-314
- Postinfarct sympathetic hyperactivity differentially stimulates expression of tyrosine hydroxylase and norepinephrine transporter.Am J Physiol Heart Circ. Physiol. 2008; 294: H99-H106
- Development of sensory neurons in the absence of NGF/TrkA signaling in vivo.Neuron. 2000; 25: 345-357
- PKA-Bad-14-3-3 and Akt-Bad-14-3-3 signaling pathways are involved in the protective effects of PACAP against ischemia/reperfusion-induced cardiomyocyte apoptosis.Regul. Pept. 2008; 145: 105-115
- Basis for the preferential activation of cardiac sympathetic nerve activity in heart failure.Proc. Natl. Acad. Sci. U. S. A. 2009; 106: 924-928
- Mechanisms of sudden cardiac death.J Clin Invest. 2005; 115: 2305-2315
- Increased cardiac adrenergic drive precedes generalized sympathetic activation in human heart failure.Circulation. 1997; 95: 169-175
- Nerve growth factor antiserum induces axotomy-like changes in neuropeptide expression in intact sympathetic and sensory neurons.J. Neurosci. 2001; 21: 363-371
- Long-distance control of synapse assembly by target-derived NGF.Neuron. 2010; 67: 422-434
- Regional sympathetic denervation after myocardial infarction in humans detected noninvasively using I-123-metaiodobenzylguanidine.J. Am. Coll. Cardiol. 1989; 14: 1519-1526
- Comparison between the effect of neuronal activity and nerve growth factor on the enzymes involved in the synthesis of norepinephrine.Pharmacol. Rev. 1972; 24: 255-267
- TRPV1 gene knockout impairs postischemic recovery in isolated perfused heart in mice.Circulation. 2005; 112: 3617-3623
- Macrophage depletion suppresses sympathetic hyperinnervation following myocardial infarction.Basic Res. Cardiol. 2009; 104: 681-693
- Mechanisms of neurotrophin receptor signalling.Biochem. Soc. Trans. 2006; 34: 607-611
- Mechanisms of cardiac nerve sprouting after myocardial infarction in dogs.Circ. Res. 2004; 95: 76-83
- Influence of myocardial ischemia and infarction on autonomic innervation of heart.Circulation. 1990; 82: 1095-1105
- Hemodynamics of anesthetized ventilated mouse models: aspects of anesthetics, fluid support, and strain.Am J Physiol Heart Circ. Physiol. 2002; 282: H2099-H2105
Article info
Publication history
Published online: June 06, 2011
Accepted:
May 11,
2011
Received in revised form:
May 9,
2011
Received:
November 8,
2010
Identification
Copyright
© 2011 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
