Comparison of the relaxing actions of acetylcholine and substance P in smooth muscle of the guinea-pig aorta.
The relationship between relaxation produced by acetylcholine (ACh) or substance P (SP) and tissue cyclic GMP content was investigated in the isolated guinea-pig aorta. ACh and SP relaxed aortic rings precontracted with noradrenaline (NA) or high-K solution ([K+]o = 38.8 mM), in an endothelium-dependent manner. The amplitude of relaxation was larger for SP than for ACh. Nitroarginine inhibited ACh-induced but not SP-induced relaxation in NA-contraction, while this chemical inhibited both ACh- and SP-induced relaxations in high-K contraction. The tissue cyclic GMP content was not changed by nitroarginine or by removal of endothelial cells, but was elevated by stimulation with NA, ACh or SP by a factor of about 3, 5 or 11 times, respectively. These actions of ACh or SP were endothelium-dependent, and were inhibited by nitroarginine and remained unaltered by high-K solution. Thus, ACh and SP relax muscles indirectly by releasing endothelial factors, and the former by releasing mainly an endothelium-derived relaxing factor (EDRF), and the latter by releasing EDRF and other unidentified factors. As the relaxing actions of the latter factors are inhibited by high-K solution with no relation to the production of cyclic GMP, an involvement of hyperpolarizing factor, possibly EDHF, is suggested.
Hozumi
T
T
Department of Physiology, Nagoya City University Medical School, Japan.
Fukuta
H
H
Suzuki
H
H
D000109:Acetylcholine / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology*; D001685:Biological Factors / Q000502:physiology; D006152:Cyclic GMP / Q000032:analysis; D004730:Endothelium, Vascular / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000032:analysis; D013373:Substance P / Q000494:pharmacology / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology
D001685:Biological Factors; D004791:Enzyme Inhibitors; C067410:endothelium-dependent hyperpolarization factor; D019335:Nitroarginine; D009569:Nitric Oxide; D013373:Substance P; D006152:Cyclic GMP; D000109:Acetylcholine; D011188:Potassium; D009638:Norepinephrine