Different K+ Channels Are Involved in Relaxation of Arterial and Venous Graft Induced by Nicorandil

The drug nicorandil is a vasodilator approved for the treatment of angina. In addition to its well-known effect on the opening of ATP-sensitive K+ (K-ATP) channels, nicorandil-induced vasorelaxation also involves the opening of Ca2+-activated K+ channels. The aim of this study was to investigate the effects of nicorandil on the isolated human internal mammary artery (HIMA) and the human saphenous vein (HSV) and to define the contribution of different K+ channel subtypes in the nicorandil action on these arterial and venous grafts. Our results show that nicorandil induced a concentration-dependent relaxation of HSV and HIMA rings precontracted by phenylephrine. Glibenclamide, a selective K-ATP channels inhibitor, partially inhibited the response to nicorandil in both HSV and HIMA. Iberiotoxin, a most selective blocker of large-conductance Ca2+-activated K+ (BKCa) channels, partly antagonized relaxation of HIMA. A nonselective blocker of voltage-gated K+ channels, 4-aminopyridine caused partial inhibition of the nicorandil-induced relaxation of HSV but did not antagonize relaxation of HIMA induced by nicorandil. Margatoxin, a potent inhibitor of K(V)1.3 channels, did not abolish the effect of nicorandil on HSV and HIMA. Our results showed that nicorandil induced strong endothelium-independent relaxation of HSV and HIMA contracted by phenylephrine. It seems that K-ATP and 4-aminopyridine-sensitive K+ channels located in the smooth muscle of HSV mediated relaxation induced by nicorandil. In addition, K-ATP and BKCa channels are probably involved in the nicorandil action on HIMA.