Possible role for cyclic GMP in endothelium-dependent relaxation of rabbit aorta by acetylcholine. Comparison with nitroglycerin.

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.