Different Effects of a Long-term Administration of β-blockers,Bopindolol and Atenolol, on the Binding Characteristics ofβ_1-and β_2-adrenoceptor Subtypes in the Kidney of SpontaneouslyHypertensive Rats (SHR)

The effects of a chronic administration of a non-selective β-blocker, bopindolol, on the binding characteristics of radiolabeled CGP-12177 (^3H-CGP12177) to each β_1-and β_2-adrenoceptor subtype in the kidney of spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were determined using the radioligand binding assay method and compared with those of a β_1-selective β-blocker, atenolol. Bopindolol (1 mg/kg/day and 3 mg/kg/day) and atenolol (50 mg/kg/day) were given to 10-week-old SHR for 12 weeks. The changes in Kd and Bmax values of β_1-and β_2-adrenoceptors in the renal membranes of SHR treated both with and without these drugs were assessed by Scatchard analysis, and Bmax values and the ratios of β_1-and β_2-adrenoceptor subtypes were also calculated from displacement curves using ICI-118,551. Bmax values of β_1- and β_2-adrenoceptors in the renal membranes of SHR were significantly higher than those of WKY. The elevated Bmax values of β_1- and β_2-adrenoceptors in renal membranes of SHR were reduced by an administration of bopindolol (1 mg/kg/day and 3 mg/kg/day) with no changes in the Kd values, these changes being especially marked in β_2-adrenoceptors. No effects of the β_1-selective antagonist atenolol on these parameters were observed. These findings showed that the non-selective antagonist bopindolol decreased the Bmax values of β-adrenoceptor subtypes in renal membranes of SHR, suggesting that this drug may partially contribute to hypotensive effects.