Diamond J, Chu E B
Res Commun Chem Pathol Pharmacol. 1983 Sep;41(3):369-81.
A possible role for cyclic GMP as a mediator of the endothelium-dependent relaxation of rabbit aorta by acetylcholine has been investigated using rabbit aortic rings with and without intact endothelium. In the presence of intact endothelial cells, acetylcholine caused marked increases in tissue levels of cyclic GMP accompanied by relaxation of the muscles. In aortic rings from which the endothelium had been removed, acetylcholine caused neither cyclic GMP elevation nor relaxation of the muscles. Acetylcholine-induced relaxation and cyclic GMP elevation in preparations with intact endothelium were both blocked by atropine. Reasonably good temporal and dose-response correlations between cyclic GMP elevation and relaxation were obtained with acetylcholine. Thus, although a causal relationship has not been definitely established, these results are consistent with the proposed role for cyclic GMP as a mediator of the endothelium-dependent relaxation of rabbit aorta by acetylcholine. In contrast to the results with acetylcholine, elevation of cyclic GMP and relaxation of aortic rings by nitroglycerin were not dependent on the presence of endothelial cells. Lower doses of nitroglycerin relaxed the muscles without elevating cyclic GMP levels. At higher concentrations of nitroglycerin, greater relaxation was obtained for a given degree of cyclic GMP elevation than was the case with acetylcholine. These results suggest that at least part of nitroglycerin's relaxant effect in this tissue is independent of cyclic GMP elevation.
利用有完整内皮和无完整内皮的兔主动脉环，研究了环磷酸鸟苷（cGMP）作为乙酰胆碱介导兔主动脉内皮依赖性舒张的一种可能作用。在有完整内皮细胞存在时，乙酰胆碱可使组织中cGMP水平显著升高，同时伴有肌肉舒张。在已去除内皮的主动脉环中，乙酰胆碱既不引起cGMP升高，也不引起肌肉舒张。阿托品可阻断有完整内皮的制剂中乙酰胆碱诱导的舒张和cGMP升高。乙酰胆碱引起的cGMP升高与舒张之间存在较好的时间和剂量反应相关性。因此，虽然尚未明确建立因果关系，但这些结果与所提出的cGMP作为乙酰胆碱介导兔主动脉内皮依赖性舒张的介质的作用是一致的。与乙酰胆碱的结果相反，硝酸甘油引起的主动脉环cGMP升高和舒张不依赖于内皮细胞的存在。较低剂量的硝酸甘油可使肌肉舒张而不升高cGMP水平。在较高浓度的硝酸甘油作用下，对于给定程度的cGMP升高，其舒张程度比乙酰胆碱作用时更大。这些结果表明，硝酸甘油在该组织中的舒张作用至少部分独立于cGMP升高。
