Insulin-induced relaxation of rat mesenteric artery is mediated by Ca(2+)-activated K(+) channels.
We tested the hypothesis that relaxation of the rat mesenteric artery in response to insulin is mediated by K(+) channels. Two concentrations of insulin (10 and 100 mU/ml) induced relaxation of the artery by 6+/-1%, 24+/-3% (mean+/-S.E.M.). Denudation of the endothelium or precontraction by KCl (30 mM), clotrimazole (10 microM), a cytochrome P450 inhibitor, charybdotoxin (30 nM) an inhibitor of large-conductance Ca(2+)-activated K(+) channels, abolished the relaxation of the artery in response to insulin. However, N(omega)-nitro-L-arginine methyl ester (L-NAME; 100 microM), an inhibitor of nitric oxide synthase, apamin (1 microM), an inhibitor of small-conductance Ca(2+)-activated K(+) channels, or glibenclamide (10 microM), an ATP-sensitive K(+) channels blocker, did not attenuate the relaxation of the artery caused by insulin. These results suggest that the relaxation of rat mesenteric artery in response to insulin is mediated mostly by large-conductance Ca(2+)-activated K(+) channels, perhaps an endothelium-derived hyperpolarizing factor (EDHF).
Iida
S
S
Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. siida@med.nihon-u.ac.jp
Taguchi
H
H
Watanabe
N
N
Kushiro
T
T
Kanmatsuse
K
K
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D003022:Clotrimazole / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D007328:Insulin; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D018999:Charybdotoxin; D010656:Phenylephrine; D001030:Apamin; D003022:Clotrimazole; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester