Ignarro L J, Burke T M, Wood K S, Wolin M S, Kadowitz P J
J Pharmacol Exp Ther. 1984 Mar;228(3):682-90.
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.
本研究的目的是检测牛肺内动脉中松弛与环磷酸鸟苷（cGMP）积累之间的关系，以响应乙酰胆碱。乙酰胆碱分别使具有完整或受损内皮细胞层的离体动脉环松弛或收缩。乙酰胆碱引起的苯肾上腺素预收缩环的松弛伴随着动脉cGMP的时间和浓度依赖性积累，但不伴随环磷酸腺苷（cAMP）的积累。松弛和cGMP积累均被阿托品和亚甲蓝拮抗。另一方面，奎纳克林拮抗松弛作用，但不改变cGMP的积累。硝酸甘油和S-亚硝基-N-乙酰青霉胺也使具有完整内皮的肺内动脉环松弛，并导致cGMP水平同时升高，但不导致cAMP水平升高。这两种作用均被亚甲蓝拮抗，但不被阿托品或奎纳克林拮抗。制备的具有受损内皮的动脉环对乙酰胆碱收缩，但对硝酸甘油和S-亚硝基-N-乙酰青霉胺松弛。乙酰胆碱引起的收缩被阿托品显著抑制，被奎纳克林部分抑制，并被亚甲蓝增强。乙酰胆碱收缩的内皮受损环中的cGMP水平升高，这被阿托品和亚甲蓝均抑制，但不被奎纳克林抑制。奎纳克林对乙酰胆碱引起的张力变化的作用似乎是非特异性的。这些观察结果表明，乙酰胆碱和含氮氧化物的血管舒张剂引起的牛肺内动脉松弛与cGMP的积累密切相关。此外，乙酰胆碱引起的收缩与cGMP积累之间似乎存在明显的分离。
