Prostaglandins and the contractile effect of angiotensin i and ii in the uterus isolated from ouariectomized rats. influence*of indo methacin and 17-β estradiol

Abstract

The purpose of the present study was to explore whether, the stimulating contractile action of angiotensin II (AII) or of angiotensin I (AI), in uterine strips isolated from rats, either spayed or spayed and injected with 17-β estradiol, was somehow linked to tissue generated prostaglandine (PGs). Indomethacin (10- 6M), shifted to the left the dose-response curve for AII in preparations from ovariectomized animals; augmenting both, the efficacy and the potency of the agonist. Dose-response curves for All were also explored in the presence of subthreshold concentrations of several exogenous PGs. PGE 2 (10-9M) completely abolished the influence of indomethacin on the cu ve for AII; PGD 2 (10-9M) did not evoke effects and PGF 2α (10 -9M) only altered the threshold dose, the rest of the curve remaining similar to that obtained with indomethacin alone. The cumulative dose-response curve for AI, in strips isolated from ovariectomized rats, was comparable to that for AII and, the presence of indomethacin, only reduced the concentration for the threshold action of AI, in comparison to controls. Captopril (100 ng/ml), shifted to the right the dose-response curve for AI and indomethacin failed to alter the effects of AI in the presence of captopril. In strips isolated from ovariectomized rats, injected with 17-β estradiol, the low concentration points of the dose-response curve for All were shifted to the left of those for the agonist in control preparations from spayed rats not treated with estradiol. Furthermore, indomethacin failed to alter the responses to AII in strips from spayed animals injected with 17-β estradiol. The foregoing results document that an inhibitor of tissue PGs synthesis,namely indomethacin, is able to modify the dose-response curve for AII, rather than that for AI, in the uterus from ovariectomized rats, but not in preparations from spayed animals treated with estrediol. This, as well as the effect of a subthreshold dose of PGs, suggest that a minimun of PGE 2 is required for the contractile influence of All and not for that of AI. Moreover, the absence of estrogen dominance appears, as well, as a crucial factor for the action of AII.