Mechanisms of endothelium-dependent responses to vasoactive agents in isolated porcine coronary arteries.
In isolated porcine coronary arteries, acetylcholine elicited contractions that were potentiated by endothelium denudation. In endothelium-intact strips, the contraction deteriorated by repeated trials and was reversed to a relaxation. NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthesis inhibitor, abolished the relaxation or reversed it to a contraction. Endothelium-dependent relaxations caused by serotonin were also reversed to a contraction by treatment with L-NA. Relaxations caused by substance P were dependent on the endothelium and were abolished by oxyhemoglobin; however, L-NA did not completely abolish the relaxation. It may be concluded that porcine coronary arteries respond to acetylcholine with contractions by a direct action on smooth muscle that are minimized by stimulated release of NO from the endothelium. It appears that the relaxation caused by serotonin is due to NO released from the endothelium, whereas the substance P-induced relaxation is associated mainly with endothelium-derived NO produced by NO synthase sensitive to L-NA and also with NO produced via a L-NA-resistant process or via a pathway distinct from that through NO synthase.
Matsumoto
T
T
Department of Pharmacology, Shiga University of Medical Sciences, Ohtsu, Japan.
Kinoshita
M
M
Toda
N
N
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine; D009638:Norepinephrine / Q000494:pharmacology; D010108:Oxyhemoglobins / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D013552:Swine
D002317:Cardiovascular Agents; D010108:Oxyhemoglobins; D019335:Nitroarginine; D009569:Nitric Oxide; D012701:Serotonin; D013373:Substance P; D000001:Calcimycin; D001120:Arginine; D000109:Acetylcholine; D009638:Norepinephrine