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 endothelium. Experiments were designed to measure both Fura-2-[Ca]i fluorescence and contractile tension simultaneously. In both preparations, ET-1 (10(-10) to 10(-7) M) induced contractions and increases of the fluorescence ratio in a concentration-dependent manner. ET-1-induced contractions and elevations of [Ca]i were blocked by the dual L- and R-type calcium-channel blocker (-)PN200 110 (10(-6) M), whereas nifedipine (10(-6) M) affected only the latter parameter. BQ-123, a selective ET(A) receptor antagonist, almost totally blocked the ET-1-induced contraction and elevation of [Ca]i. Our results illustrate the activation of the R-type calcium channel by ET-1 on the smooth muscle and on the endothelium rabbit aorta. This effect of ET-1 on the R-type calcium channel is mediated by ET(A) and ETB receptor stimulation.