Nitric oxide mediates vasoactive effects of endothelin-3 on rat mesenteric microvascular beds in vivo.
In order to clarify whether the vasoactive effects of endothelin-3 (ET-3) on microvessels are associated with the endothelium-derived relaxing factor (EDRF) in vivo, the authors examined the effects of L-NG-monomethyl arginine (L-NMMA), an analog of L-arginine, on low-dose ET-3 induced hemodynamic changes in the mesenteric microcirculation of male Wistar rats. The intravital observation revealed that ET-3 100 pM induced a remarkable and periodic vasoconstriction in arterioles, and the constriction was sustained for approximately fifteen minutes. No remarkable change was observed in the microvessels after the superfusion of 1 pM ET-3. Superfusion of 1 pM ET-3 with 100 microM L-NMMA elicited the vasoconstriction in arterioles, and the arteriolar diameter recovered to the control level within ten minutes in spite of continuing the superfusion. The vasoconstriction induced by low-dose ET-3 with L-NMMA was suppressed by the additional superfusion of 200 microM L-arginine. The present study suggests that the recovery of arteriolar diameter after the ET-3-induced constriction may be mediated by nitric oxide at least in the early phase.
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
I
I
Kurose
D
D
Fukumura
S
S
Miura
E
E
Sekizuka
H
H
Nagata
M
M
Suematsu
M
M
Tsuchiya
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016232:Endothelins / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D019323:omega-N-Methylarginine
D016232:Endothelins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine