Interaction of endothelin and Ca++ entry blockers on renal circulation in anesthetized rabbits

We examined an interaction of endothelium-derived vasoconstrictor endothelin and Ca++ entry blockers on renal blood flow in anesthetized rabbits. A bolus intrarenal arterial injection of endothelin at doses of 10, 25 and 50 ng produced a decrease in renal blood flow with a dose-dependent fashion, while there was no change in systemic arterial pressure. A similar extent of the decrease in renal blood flow was produced at doses of endothelin 50 ng(2.0 x 10(-11)M), angiotensin II 10 ng (9.7 x 10(-12)M) and norepinephrine 250 ng (1.5 x 10(-9)M), although the decrease in renal blood flow by endothelin was sustained in contrast to angiotensin II or norepinephrine. Pretreatment with Ca++ entry blocker nifedipine (1.0 microgram/kg/min) or diltiazem (20 micrograms/kg/min) attenuated the decrease in renal blood flow and reduced the duration time. These results suggest that exogenous endothelin produces a renal vasoconstriction in vivo. However, it seems that endothelin is less potent than angiotensin II in renal circulation in anesthetized rabbits. It is also indicated that the decrease in renal blood flow by endothelin could be mediated through a common Ca++ channel pathway in renal vasculatures.