Mechanisms for the Inhibition of Vasopressin-Stimulated Water Flow by Captopril in the Toad Bladder

Abstract

The mechanisms by which captopril inhibits vasopressin-stimulated osmotic water flow in the toad bladder have been investigated in vitro. Captopril has two possible mechanisms for the inhibitory action on the water flow, one is its stimulative effect on prostaglandin E2 (PGE2) biosynthesis by inhibition of kininase II activity, the other, is a direct effect on water flow independent of PGE2. Captopril inhibited the vasopressin-, cyclic adenosine monophosphate- and 3-isobutyl-1-methyl-xanthine-stimulated water flow. The inhibition of water flow by bradykinin was enhanced by captopril. These data indicate that captopril increased the amount of bradykinin in toad bladder cells resulting in the production of PGE2 which inhibited the increase in water flow induced by vasopressin. The inhibitory effect of captopril, however, also occurred in the presence of indomethacin, when the production of PGE2 was attenuated. Thus, it was concluded that captopril inhibits the vasopressin-stimulated water flow indirectly by inhibiting the degradation of bradykinin and thereby enhancing the production of PGE2, and directly at a site following the production of cyclic adenosine monophosphate by vasopressin.