The involvement of K-Ca, K-ATP and K-V channels in vasorelaxing responses to acetylcholine in rat aortic rings

1. In rat aortic rings contracted by phenylephrine, acetylcholine relaxation was partly inhibited by: iberiotoxin, a Ca2+-activated K(K-Ca) channel inhibitor; glyburide, an ATP-dependent K(K-ATP) channel inhibitor; and 4-aminopyridine, a voltage dependent K(K-V) channel inhibitor, and was almost abolished by the removal of endothelium. 2. N-G-nitro-L-arginine (NOARG), a NO synthase inhibitor, markedly reduced acetylcholine relaxation and abolished the inhibitory effects of iberiotoxin and glyburide on the acetylcholine relaxation. The inhibitory effect of 4-aminopyridine on acetylcholine relaxation was partly reduced by NOARG. 3. Methylene blue, a guanylate cyclase inhibitor, markedly inhibited acetylcholine relaxation and also abolished the inhibitory effects of iberiotoxin and glyburide and partly inhibited that of 4-aminopyridine on acetylcholine relaxation. 4. Metyrapone, a cytochrome P-450-dependent monooxygenase inhibitor, and AA861, a 5-lipoxygenase inhibitor, but not indomethacin, a cyclooxygenase inhibitor, partly inhibited acetylcholine relaxation and reduced the inhibitory effect of 4-aminopyridine on acetylcholine relaxation. 5. These results indicate that, in rat aortic rings, acetylcholine relaxation may be dependent on the activation of K-Ca, K-ATP and K-V channels. The activations of K-Ca and K-ATP channels may also be dependent on NO synthesis and subsequent formation of cGMP. The activation of K-V channels may also be dependent on NO synthesis and subsequent activation of guanylate cyclase. In addition, the activation of K-V channels may be dependent on the metabolism of arachidonic acid through 5-lipoxygenase and cytochrome P-450-dependent monooxygenase pathways. Copyright (C) 1997 Elsevier Science Inc.