NITRIC-OXIDE MEDIATES VASOACTIVE EFFECTS OF ENDOTHELIN-3 ON RAT MESENTERIC MICROVASCULAR BEDS INVIVO

In order to clarify whether the vasoactive effects of endothelin-3 (ET -3) on microvessels are associated with the endothelium-derived relaxi ng factor (EDRF) in vivo, the authors examined the effects of L-N(G)-m onomethyl arginine (L-NMMA), an analog of L-arginine, on low-dose ET-3 induced hemodynamic changes in the mesenteric microcirculation of mal e Wistar rats. The intravital observation revealed that ET-3 100 pM in duced a remarkable and periodic vasoconstriction in arterioles, and th e constriction was sustained for approximately fifteen minutes. No rem arkable change was observed in the microvessels after the superfusion of 1 pM ET-3. Superfusion of 1 pM ET-3 with 100 muM L-NMMA elicited th e vasoconstriction in arterioles, and the arteriolar diameter recovere d to the control level within ten minutes in spite of continuing the s uperfusion. The vasoconstriction induced by low-dose ET-3 with L-NMMA was suppressed by the additional superfusion of 200 muM L-arginine. Th e present study suggests that the recovery of arteriolar diameter afte r the ET-3-induced constriction may be mediated by nitric oxide at lea st in the early phase.