BETA-ADRENOCEPTOR ACTIVATION STIMULATES, AND PHOSPHODIESTERASE INHIBITION POTENTIATES, PLACENTAL PRORENIN SYNTHESIS AND RELEASE

This study evaluated activation of beta-adrenoceptors and the cAMP pat hway on prorenin secretion from human placental explants. For comparat ive purposes, hCG secretion was also measured. Treatment with selectiv e beta-adrenergic agonists (beta(1)-dobutamine and beta(2)-terbutaline ) produced dose-dependent increases in prorenin secretion, with dobuta mine yielding a greater response (10- vs. 6-fold). In contrast, hCG se cretion was stimulated only by terbutaline (5-fold). Prorenin and hCG secretory responses were inhibited by corresponding selective receptor antagonists (beta(1)-metoprolol and beta(2)-ICI 118,551). Selective p hosphodiesterase inhibitors were used to evaluate the role of cAMP in mediating these responses. Marked potentiation of beta-adrenoceptor-de pendent prorenin secretion was observed with the type III inhibitor, c ilostamide (63-76%), and the type IV inhibitor, Re-201724 (32-43%). Ty pe I (8-methoxymethyl-3-isobutylmethylxanthine) and type V inhibitors (dipyridamole and M and B 22,948) showed no potentiation. These studie s demonstrate that activation of both beta(1)- and beta(2)-receptors s timulates placental prorenin release. The potentiation of beta-adrener gically activated prorenin release by selective inhibitors of phosphod iesterase indicates a coupling of beta-adrenoceptor and adenylate cycl ase. The contrast in secretion of prorenin and hCG by selective beta-a drenergic agonists suggests differences in cellular localization. The results indicate that clinically used adrenergic agonists can affect t he placental renin-angiotensin system. The role of endogenous activato rs of beta-adrenoceptors in this system remains to be determined.