Effect of Bopindolol on Renin Secretion and Renal Excretory Function in Rats

Abstract

We investigated the effects of the new beta-adrenoceptor antagonist, bopindolol, on stimulated renin secretion and on renal function in conscious rats. Intravenous doses of 10, 31.6, and 100 micrograms/kg of bopindolol antagonized the rise in plasma renin activity (PRA) induced by the administration of isoproterenol (10 micrograms/kg, s.c.). Peak PRA, evident at 15 min after isoproterenol, reached 27 +/- 3 ng/ml/h with bopindolol (100 micrograms/kg) pretreatment vs. 105 +/- 7 ng/ml/h in saline controls. Antagonism by bopindolol (100 micrograms/kg, i.v.) of isoproterenol-stimulated rise in PRA persisted through 12 h. Within this dosage range, bopindolol itself had no significant effect on PRA. Significant antagonism of beta-adrenoceptor-induced hypotension resulted with 31.6 and 100 micrograms/kg of i.v. bopindolol. Orally administered bopindolol produced significant antagonism of isoproterenol-induced increase in PRA at a dose of 316 micrograms/kg; however, oral doses of 31.6-316 micrograms/kg of bopindolol failed to significantly alter furosemide-stimulated increase in PRA. Bopindolol alone had little effect on renal excretory function but caused a slight attenuation of furosemide-induced diuresis and electrolyte excretion. Plasma electrolytes and osmolarity were unaffected by bopindolol alone or in conjunction with furosemide. These results indicate that bopindolol (a) is a potent, long-acting, orally active, antagonist of beta-adrenoceptor-stimulated renin secretion in the rat, (b) is ineffective in antagonizing furosemide-induced rise in PRA, (c) does not elevate basal levels of PRA by virtue of its intrinsic sympathomimetic activity, and (d) does not cause dramatic alteration of renal excretory function at effective beta-blocking doses.