Effects of Chronic Administration of Bopindolol on the Binding Characteristics of Cardiac α_1H-, α_1L-, β₁- and β₂-Adrenoceptor Subtypes in Cardiac Muscles of Spontaneously Hypertensive Rats (SHR)

Abstract

The effects of the chronic administration of bopindolol on the binding characteristics of [³H]CGP12177 and [³H]prazosin to cardiac α_1H-, α_1L-, β₁- and β₂-adrenoceptor subtypes of spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were compared with those of two other β-blockers, atenolol and propranolol. Bopindolol (1 and 3 mg/kg/d), atenolol (50 mg/kg/d) and propranolol (60 mg/kg/d) were given to 10-week-old SHR for 12 weeks. The changes in K_d and B_max values of the myocardium of SHR treated without and with those drugs were assessed by Scatchard analysis, and the ratio and B_max values of the β₁- and β₂-adrenoceptor subtypes were also calculated from displacemental curves using ICI 118, 551. The systolic blood pressure in SHR was dose-dependently lowered by the administration of dopindolol, and was also lowered by the administration of atenolol and propranolol. The B_max values of β₁- and β₂-adrenoceptors were lowered by the administration of bopindolol (1 and 3 mg/kg/d) without any changes in the K_d values or the ratio of β₁- and β₂-adrenoceptors. Propranolol lowered 3-fold the affinity to the β-adrenoceptor. On the other hand, the K_d and B_max values of α_1H- and α_1L-adrenoceptor subtypes (high and low affinity binding sites for [³H]prazosin) were not changed by these drugs. These findings suggest that bopidolol had a beneficial effect on β-adrenoceptors in the membranes of cardiac muscles of SHR, simplying that these effects may contribute to lowering hypertension.