Different effects of R 56865 and calcium entry blockers on K+- and noradrenaline-induced contractions and45Ca uptake in rat aorta

The effects of R 56865, nifedipine, verapamil, diltiazem and flunarizine on K+- and NA-induced contractions and K+-induced45Ca uptake were compared in the isolated rat aorta. The calcium entry blockers concentration dependently inhibited the K+-induced contraction and45Ca uptake over the same dose-range. R 56865 inhibited the K+-induced45Ca uptake, but only partly inhibited the K+-induced contraction. The calcium entry blockers caused a slight rightward shift and a depression of the maximum of the concentration-response curve for the NA-induced contraction. In contrast, R 56865 caused a strong, dose-dependent rightward shift and a depression of the maximum, 10-6and 10-5M being equieffective. The effects of R 56865 and nifedipine were independent of each other. Nevertheless, the NA-induced increase in45Ca uptake, a putative model for Ca influx, was attenuated by R 56865. In conclusion, R 56865 is a weak inhibitor of the K+-induced Ca influx but is without effect on the NA-induced Ca influx. The discrepancy between its effects on K+-induced contractions and45Ca uptake may be explained by an inhibition of the uptake of45Ca from the cytosol into the45Ca pool. The interaction between R 56865 and the α1-adrenoceptor-mediated contractions may be explained by an action at a site that is distinct from the NA-binding-site on the α1-adrenoceptor