Substance P evokes bradycardia by stimulation of postganglionic cholinergic neurons.
Substance P (SP) evokes bradycardia that is mediated by cholinergic neurons in experiments with isolated guinea pig hearts. This project investigates the negative chronotropic action of SP in vivo. Guinea pigs were anesthetized with urethane, vagotomized and artificially respired. Using this model, IV injection of SP (32 nmol/kg/50 microl saline) caused a brief decrease in heart rate (-30+/-3 beats/min from a baseline of 256+/-4 beats/min, n = 27) and a long-lasting decrease in blood pressure (-28+/-2 mmHg from baseline of 51+/-5 mmHg, n = 27). The negative chronotropic response to SP was attenuated by muscarinic receptor blockade with atropine (-29 +/- 9 beats/min before vs -8 +/- 2 beats/min after treatment, P = 0.0204, n = 5) and augmented by inhibition of cholinesterases with physostigmine (-23 +/- 6 beats/min before versus -74 +/- 20 beats/min after treatment, P = 0.0250, n = 5). Ganglion blockade with chlorisondamine did not diminish the negative chronotropic response to SP. In another series of experiments, animals were anesthetized with sodium pentobarbital or urethane and studied with or without vagotomy. Neither anesthetic nor vagotomy had a significant effect on the negative chronotropic response to SP (F3,24 = 1.97, P = 0.2198). Comparison of responses to 640 nmol/kg nitroprusside and 32 nmol/kg SP demonstrated that the bradycardic effect of SP occurs independent of vasodilation. These results suggest that SP can evoke bradycardia in vivo through stimulation of postganglionic cholinergic neurons.
Tompkins
J D
JD
Department of Pharmacology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City 37614, USA.
Hoover
D B
DB
Hancock
J C
JC
D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001338:Autonomic Fibers, Postganglionic / Q000187:drug effects*; D001919:Bradycardia / Q000139:chemically induced*; D002714:Chlorisondamine / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004347:Drug Interactions; D005724:Ganglia / Q000187:drug effects*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D011950:Receptors, Cholinergic; D013373:Substance P / Q000494:pharmacology*; D014520:Urethane / Q000494:pharmacology
D000777:Anesthetics; D002800:Cholinesterase Inhibitors; D018727:Muscarinic Antagonists; D011950:Receptors, Cholinergic; D009599:Nitroprusside; D013373:Substance P; D014520:Urethane; D001285:Atropine; D010830:Physostigmine; D010424:Pentobarbital; D002714:Chlorisondamine