Nicorandil: Differential Contribution of K Channel Opening and Guanylate Cyclase Stimulation to its Vasorelaxant Effects on Various Endothelin-1-Contracted Arterial Preparations.

In endothelium-denuded rat aortic rings, the sustained contractile effects produced by endothelin-1 (ET-1; 3.2 nM) were concentra-tion-dependently overcome by nicorandil, aprikalim (RP 52891), a specific K channel opener, and nitroglycerin, a stimulant of guanylate cyclase (EC: 2.55 ± 0.06, 0.37 ± 0.05 and 0.3 ± 0.008 M respectively, n = 13-16/group). The decontractant activity of aprikalim was not affected by the guanylate cyclase inhibitor methylene blue (1 0 zM), whereas it was markedly an-tagonized by glibenclamide (1 tiM) (pK8: 7.1 9 ± 0.1 5), an antag-onist of ATP-gated K channels in pancreatic $ cells. This sulfo-nylurea failed to modify nitroglycerin-induced effects, but slightly reduced (10-15%) those produced by high concentrations of nicorandil. By contrast, methylene blue significantly displaced (4-fold) the control concentration-vasorelaxant response curve