Inhibitory effects of amiloride on alpha adrenoceptors in canine vascular smooth muscle.

Amiloride inhibits vascular smooth muscle contractions from canine aorta and saphenous vein. The mechanisms were studied using radioligand binding and functional techniques. Amiloride inhibited [3H]prazosin and [3H]rauwolscine binding to alpha-1 and alpha-2 adrenoceptors in a concentration-dependent manner. Amiloride increased Kd values for [3H]rauwolscine without affecting the maximum binding of [3H]prazosin. These results suggest that the drug interacts with the alpha-1 adrenoceptor binding sites in a competitive manner and with the alpha-2 adrenoceptor binding sites in a noncompetitive manner. Amiloride reduced maximal contractile responses to agonists selective for both alpha adrenoceptors and to elevated K+, the EC50 values were increased by about 10-fold in the presence of amiloride. In Ca+(+)-free Krebs' solution, contractions induced in saphenous vein after addition of Ca++ in saphenous vein in the presence of adrenoceptor agonists were inhibited by amiloride. Our results suggest that amiloride reduced alpha-1 and alpha-2 adrenoceptor-mediated responses and inhibited Ca++ influx.