R-TYPE CALCIUM-CHANNEL INVOLVED IN ENDOTHELIN-1-INDUCED CONTRACTION OF RABBIT AORTA

The mechanism of Ca2+ mobilization induced by endothelin-1 (ET-1) and the receptor subtype responsible for this effect were examined in the rabbit aorta. We have used preparations with intact and denuded endoth elium. Experiments were designed to measure both Fura-2-[Ca](i) fluore scence and contractile tension simultaneously. In both preparations, E T-1 (10(-10) to 10(-7) M) induced contractions and increases of the fl uorescence ratio in a concentration-dependent manner. ET-1-induced con tractions and elevations of [Ca](i) were blocked by the dual L- and R- type calcium-channel blocker (-)PN200 110 (10(-6) M), whereas nifedipi ne (10(-6) M) affected only the latter parameter. BQ-123, a selective ET(A) receptor antagonist, almost totally blocked the ET-1-induced con traction and elevation of [Ca](i). Our results illustrate the activati on of the R-type calcium channel by ET-1 on the smooth muscle and on t he endothelium rabbit aorta. This effect of ET-1 on the R-type calcium channel is mediated by ET(A) and ET(B) receptor stimulation.