Substance P modulates autonomic nerve activity in canine hearts.
We examined the hypothesis that substance P (SP) acts as an "afferent neuromodulator" in the heart regulating the response of the cardiac autonomic nerves to reflexes originating in the heart. We employed the acute, isovolumic canine heart preparation in which the amplitude of the chamber pressure accurately reflects changes in contractility. The heart was decentralized except for one-half of the right vagus, which was left intact to permit afferent communication with the central nervous system, while the remaining one-half was tightly ligated so that the distal part could be used for efferent stimulation. SP was injected in doses of 2-10 micrograms ic. There were no significant inotropic responses to 2 and 5 micrograms SP, whereas 10 micrograms produced positive inotropy of 5-15%. When vagal tone was elevated with sustained vagal stimulation, the same doses of SP increased contractility by 12-28%. Similarly, during right stellate ganglion stimulation (SS), SP decreased contractility 8-22%. After the intact half of the right vagus was sectioned, SP modulation of vagal responses was unaffected, while modulation of atrial, but not ventricular, responses to SS was significantly attenuated. When tested on a series of cardiac-denervated dogs, SP had no effect on cardiac inotropy at any dose. However, when contractility was increased with isoproterenol infusion, SP caused a small decrease in ventricular contractility. These results suggest that SP acts as a modulator of cardiac autonomic neural tone. It is possible that the neuropeptide is released from intramyocardial afferent collateral fibers and inhibits the elevation in vagal or sympathetic nerve activity initiated by activation of cardiac primary afferent nerves.
Smith
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DC
Department of Physiology, University of New Mexico School of Medicine, Albuquerque 87131.
Priola
D V
DV
Blomquist
T M
TM
D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects*; D002304:Cardiac Pacing, Artificial; D003714:Denervation; D004285:Dogs; D006329:Heart Conduction System / Q000187:drug effects*; D013373:Substance P / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology
D013373:Substance P