β-Adrenergic System Is Modified in Compensatory Pressure Cardiac Overload in Rats

Abstract

The beta-adrenergic system has been explored in cardiac hypertrophy (CH) by combining an in vitro study of the inotropic effect of isoproterenol (ISO) and of forskolin (FSK) and binding assays using radioactive pindolol. CH was obtained within 4-6 weeks by banding the abdominal aorta which results in an increase in left ventricular (LV) weight [743 +/- 14 and 1,098 +/- 24 mg in sham-operated (SH) and in CH, respectively, p less than 0.01] and in the LV wt/body wt ratio (2.14 +/- 0.05 and 3.24 +/- 0.05, p less than 0.001). The inotropic effect was evaluated on an isolated Langendorff heart preparation whose coronary flow was normalized per gram of tissue either by using different constant coronary pressures (75 and 110 mm Hg in SH and in CH, respectively) or different constant coronary flows (15 and 20 ml min-1 in SH and CH, respectively). Binding assays were performed using 125I pindolol, a rather crude preparation of sarcolemma and a LIGAND program for calculation. (i) The inotropic responsiveness to both ISO and FSK is depressed by approximately 30% in CH, at any drug concentration, without change in EC50 whatever the technique used to perfuse the tissue. The time course of the process is slower but, in the case of ISO, remains biphasic. (ii) Binding assays show a normal affinity (Kd 100 pM) while receptor density is depressed (32 +/- 3 and 25 +/- 2 fmol mg protein-1, p less than 0.05 or 3,287 +/- 312 and 2,000 +/- 163 fmol/g fresh tissue, p less than 0.01, in SH and CH, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)