Abstract
AbstractMyocardial ischemia evokes powerful reflex responses through activation of vagal and sympathetic afferents in the heart through the release of ischemic metabolites. We have demonstrated that extracellular ATP stimulates cardiac sympathetic afferents through P2 receptor-mediated mechanism, and that opioid peptides suppress these afferents’ activity. However, the roles of both P2 receptor and endogenous opioids in cardiac sympathoexcitatory reflex (CSR) responses remain unclear. We therefore hypothesized that activation of cardiac P2 receptor evokes CSR responses by stimulating cardiac sympathetic afferents and these CSR responses are modulated by endogenous opioids. We observed that intrapericardial injection of α,β-methylene ATP (α,β-meATP, P2X receptor agonist), but not ADP (P2Y receptor agonist), caused a graded increase in mean arterial pressure in rats with sinoaortic denervation and vagotomy. This effect of α,β-meATP was abolished by blockade of cardiac neural transmission with intrapericardial procaine treatment and eliminated by intrapericardial A-317491, a selective P2X2/3 and P2X3 receptor antagonist. Intrapericardial α,β-meATP also evoked CSR response in vagus-intact rats. Furthermore, the P2X receptor-mediated CSR responses were enhanced by intrapericardial naloxone, a specific opioid receptor antagonist. These data suggest that stimulation of cardiac P2X2/3 and P2X3, but not P2Y receptors, powerfully evokes CSR responses through activation of cardiac spinal afferents, and that endogenous opioids suppress the P2X receptor-mediated CSR responses.
Funder
U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute
U.S. Department of Health & Human Services | NIH | National Center for Complementary and Integrative Health
Publisher
Springer Science and Business Media LLC
Reference78 articles.
1. Weaver, L. C., Danos, L. M., Oehl, R. S. & Meckler, R. L. Contrasting reflex influences of cardiac afferent nerves during coronary occlusion. Am J Physiol 240, H620–H629 (1981).
2. Xu, J., Kussmaul, W., Kurnik, P. B., Al-Ahdav, M. & Pelleg, A. Electrophysiological-anatomic correlates of ATP-triggered vagal reflex in the dog. V. Role of purinergic receptors. Am J Physiol Regul. Integr. Comp Physiol 288, R651–R655 (2005).
3. Fu, L.-W., Phan, A. & Longhurst, J. C. Myocardial ischemia-mediated excitatory reflexes: a new function for thromboxane A2? Am. J. Physiol. 295, H2530–H2540 (2008).
4. Kliks, B., Burgess, M. & Abildskov, J. Influence of sympathetic tone on ventricular fibrillation threshold during experimental coronary occlusion. Am J Cardiol 36, 45–49 (1975).
5. Malliani, A., Schwartz, P. J. & Zanchetti, A. A sympathetic reflex elicited by experimental coronary occlusion. Am J Physiol 217, 703–709 (1969).
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