NITRIC-OXIDE IS THE MEDIATOR OF BOTH ENDOTHELIUM-DEPENDENT RELAXATIONAND HYPERPOLARIZATION OF THE RABBIT CAROTID-ARTERY

It is controversial whether the endothelial cell release of nitric oxi de (NO) or a different factor(s) accounts for endothelium-dependent hy perpolarization, because in many arteries endothelium-dependent relaxa tion and hyperpolarization resists inhibitors of NO synthase. The cont ribution of NO to acetylcholine-induced endothelium-dependent hyperpol arization and relaxation of the rabbit carotid artery was determined b y measuring NO with electrochemical and chemiluminescence techniques. In the presence of phenylephrine to depolarize and contract the smooth muscle cells, acetylcholine caused concentration-dependent hyperpolar ization and relaxation which were closely correlated to the release of NO. N-omega-nitro-L-arginine methyl ester (30 mu M) partially reduced the release of NO and caused a similar reduction in smooth muscle cel l relaxation and hyperpolarization. To determine if the residual respo nses were mediated by another endothelium-derived mediator or NO relea sed despite treatment with N-omega-nitro-L-arginine methyl ester, N-om ega-nitro-L-arginine (300 mu M) was added. The combined inhibitors fur ther reduced, but did not eliminate, NO release, smooth muscle relaxat ion, and hyperpolarization. Hyperpolarization and relaxation to acetyl choline remained closely correlated with the release of NO in the pres ence of the inhibitors. In addition, the NO donor, SIN-1, caused hyper polarization and relaxation which correlated with the concentrations o f NO that it released. These studies indicate that (i) the release of NO by acetylcholine is only partially inhibited by these inhibitors of NO synthase when used even at high concentrations, and (ii) NO rather than another factor accounts fully for endothelium-dependent response s of the rabbit carotid artery.