The dog common carotid artery: a sensitive bioassay for studying vasodilator effects of substance P and of kinins

Abstract

To develop a sensitive pharmacological preparation which would allow the measurement of the inhibitory effects of kinins and substance P (SP) in vascular smooth muscles, several large arteries of the dog were studied in vitro. The common carotid artery was one of the most sensitive preparations to SP and kinins. When contracted with low concentrations of noradrenaline [norepinephrine, between 3.0 .times. 10-8 and 3.0 .times. 10-7 M] this artery responds to SP (6.5 .times. 10-11 to 6.5 .times. 10-9 M) and bradykinin (BK, 8.1 .times. 10-11 to 9.1 .times. 10-8 M) with relaxations that are proportional to the concentrations of the 2 peptides. SP and BK appear to exert their relaxant effects through the activation of specific receptors as the exposure of the common carotid artery to concentrations of [Leu8]-angiotensin II, propranolol, methylsergide, cimetidine or atropine sufficient to inhibit the effects of the corresponding agonists do not affect the relaxing effect of SP and BK. [Leu8]-dis-Arg9-BK (1.0 .times. 10-6 M), indomethacin (2.8 .times. 10-5 M) and lioresal (4.7 .times. 10-5 M) are inactive. When the dog common carotid artery is desensitized with high concentrations of SP, BK, eledoisin and physalaemin a cross-desensitization is observed between SP and physalaemin. SP and kinins apparently act on different receptors. The order of potency of kinins is BK = [Tyr(Me)8]-BK > des-Arg9-BK. Apparently the receptor for kinins is of the B2 type. The order of potency of peptides related to SP is SP > C-terminal 4-11 > C-terminal hexapeptide 6-11, similar to that observed in other vascular preparations. The dog common carotid artery evidently is a preparation sensitive to SP and BK and is useful for studying the relaxant effect of these peptides on vascular smooth muscles.