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.