Association between cyclic GMP accumulation and acetylcholine-elicited relaxation of bovine intrapulmonary artery.
The objective of this study was to examine the relationship between relaxation and cyclic GMP accumulation in bovine intrapulmonary artery in response to acetylcholine. Acetylcholine relaxed or contracted isolated arterial rings possessing an intact or damaged endothelial layer, respectively. Acetylcholine-elicited relaxation of phenylephrine-precontracted rings was accompanied by a time- and concentration-dependent accumulation of arterial cyclic GMP but not of cyclic AMP. Relaxation and cyclic GMP accumulation were both antagonized by atropine and methylene blue. Quinacrine, on the other hand, antagonized relaxation without altering the accumulation of cyclic GMP. Nitroglycerin and S-nitroso-N-acetylpenicillamine also relaxed intrapulmonary rings possessing an intact endothelium and caused a concomitant rise in cyclic GMP but not cyclic AMP levels. Both effects were antagonized by methylene blue but not by atropine or quinacrine. Arterial rings prepared with damaged endothelium contracted to acetylcholine but relaxed to nitroglycerin and S-nitroso-N-acetylpenicillamine. Acetylcholine-elicited contraction was markedly inhibited by atropine, partially inhibited by quinacrine and potentiated by methylene blue. Cyclic GMP levels were increased in endothelium-damaged rings contracted by acetylcholine and this was inhibited both by atropine and methylene blue but not by quinacrine. The effects of quinacrine on acetylcholine-elicited changes in tone appear to be nonspecific. These observations indicate that relaxation of bovine intrapulmonary artery by both acetylcholine and nitrogen oxide-containing vasodilators is closely associated with the accumulation of cyclic GMP. Moreover, there appears to be a clear dissociation between contraction and cyclic GMP accumulation elicited by acetylcholine.
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000502:physiology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D005996:Nitroglycerin / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism; D011796:Quinacrine / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine
D026423:S-Nitroso-N-Acetylpenicillamine; D000242:Cyclic AMP; D005996:Nitroglycerin; D010396:Penicillamine; D011796:Quinacrine; D006152:Cyclic GMP; D000109:Acetylcholine