Effects of substance P on rate and perfusion pressure in the isolated guinea pig heart.
Negative chronotropic and vasodilator responses of the isolated perfused guinea pig heart to substance P (SP) were evaluated. Bolus injections of 2.5, 25 and 125 nmol of SP caused a dose-dependent bradycardia, with the largest dose decreasing heart rate by 53% of base line. Pretreatment with 1 microM atropine blocked the negative chronotropic response to 25 nmol of SP. Pretreatment with 0.5 microM neostigmine lowered base-line heart rate and potentiated the negative chronotropic response to 25 nmol of SP. A potent vasodilator response to SP was demonstrated after elevation of base-line perfusion pressure with 1 microM [Arg8]vasopressin or 40 mM KCl. The vasodilator effect of SP was dose-dependent and occurred at much lower doses than required to affect heart rate. The ED50 for vasodilation was less than 1 pmol in both preparations. In hearts with vascular tone increased by vasopressin, atropine (1 microM) decreased the maximum vasodilator response to SP by 23%, but neither atropine nor a combination of 10 microM cimetidine and 1 microM chlorpheniramine affected the ED50 for SP. These results suggest that SP causes bradycardia by stimulating cholinergic neurons and coronary vasodilation by some mechanism not involving either acetylcholine or histamine. Acetylcholine may, however, contribute to the maximum vasodilator response to SP.
Department of Pharmacology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City.
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Hoover
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009388:Neostigmine / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology*; D013618:Tachyphylaxis; D014664:Vasodilation / Q000187:drug effects*
D001127:Arginine Vasopressin; D013373:Substance P; D009388:Neostigmine; D001285:Atropine