A role of ion channels in the endothelium-independent relaxation of rat mesenteric artery induced by resveratrol.
Recently it has been suggested that resveratrol relaxes different isolated arteries. The present study addressed the question whether different ion channels are involved in the endothelium-independent mechanism of vasodilatation induced by resveratrol. For that purpose, we tested the action of resveratrol on the rat mesenteric artery without endothelium. Resveratrol induced concentration-dependent relaxation of rat mesenteric artery. Among the K(+)-channel blockers, 4-amynopiridine (4-AP) moderately antagonized the resveratrol-induced relaxation, while glibenclamide, tetraethylammonium chloride, charybdotoxin, margatoxin, and barium chloride did not inhibit resveratrol-induced vasorelaxation. In rings, precontracted with 100 mM K(+), the relaxant responses to resveratrol were highly significantly shifted to the right compared to those obtained in rings precontracted with phenylephrine, but resveratrol-induced maximal relaxation was only slightly affected. In order to minimize the influence of K(+) channels and voltage-gated Ca(2+) channels (VGCCs) in vascular smooth muscle, the third contraction was made by 100 mM K(+) in the presence of nifedipine. The relaxant response to resveratrol was abolished. Thus, the mechanism of vasorelaxation induced by resveratrol probably involves activation of 4-AP-sensitive K(+) channels. Its ability to completely relax the mesenteric artery precontracted with K(+)-rich solution suggests that K(+) channel-independent mechanism(s) are involved in its vasorelaxant effect. It seems that interaction with VGCCs plays a part in this K(+) channel-independent effect of resveratrol.
Gojkovic-Bukarica
Ljiljana
L
Department of Clinical Pharmacology, Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia. bukarica@rcub.bg.ac.yu
Novakovic
Aleksandra
A
Kanjuh
Vladimir
V
Bumbasirevic
Marko
M
Lesic
Aleksandar
A
Heinle
Helmut
H
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014665:Vasodilator Agents
D002121:Calcium Channel Blockers; D007473:Ion Channels; D026902:Potassium Channel Blockers; D013267:Stilbenes; D014665:Vasodilator Agents; D009543:Nifedipine; D000077185:Resveratrol; D011188:Potassium