The involvement of KCa, KATP and KV 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 Ca(2+)-activated K(KCa) channel inhibitor; glyburide, an ATP-dependent K(KATP) channel inhibitor; and 4-aminopyridine, a voltage-dependent K(KV) channel inhibitor, and was almost abolished by the removal of endothelium. 2. NG-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-amino-pyridine 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 KCa, KATP and KV channels. The activations of KCa and KATP channels may also be dependent on NO synthesis and subsequent formation of cGMP. The activation of KV channels may also be dependent on NO synthesis and subsequent activation of guanylate cyclase. In addition, the activation of KV channels may be dependent on the metabolism of arachidonic acid through 5-lipoxygenase and cytochrome P-450-dependent on the monooxygenase pathways.
Satake
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N
Department of Pharmacology, University of Hawaii, School of Medicine, Honolulu 96822, USA.
Shibata
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M
Shibata
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S
D015761:4-Aminopyridine / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D006152:Cyclic GMP / Q000096:biosynthesis; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation
D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D009569:Nitric Oxide; C064719:iberiotoxin; D015761:4-Aminopyridine; D006152:Cyclic GMP; D000109:Acetylcholine; D005905:Glyburide