Regulation of cardiac β-adrenergic receptors by captopril: Implications for congestive heart failure

Abstract

The interaction of the renin-angiotensin system and the sympathetic nervous system in patients with congestive heart failure is not well understood. We tested the hypothesis that angiotensin-converting enzyme inhibitors can resensitize the β-adrenergic receptor system. Guinea pigs were given captopril, isoproterenol, or both for 2 weeks. At death, cardiac sarcolemmal and light vesicle fractions and intact mononuclear leukocytes were prepared. Captopril treatment led to an up-regulation of cardiac β1- but not mononuclear leukocyte β2-adrenergic receptors and an increase in isoproterenol-stimulated adenylate cyclase activity in the heart. Animals treated with isoproterenol developed cardiac hypertrophy, had increased plasma norepinephrine levels, and had a decreased number and responsiveness of both cardiac and mononuclear leukocyte β-adrenergic receptors. Concomitant treatment with captopril attenuated alterations of heart weight, plasma norepinephrine levels, and cardiac β-receptor density and function. In contrast to its cardiac effects, captopril treatment did not diminish the down-regulation of mononuclear leukocyte β2-adrenergic receptors by isoproterenol. Our data suggest that captopril may resensitize the cardiac but not the mononuclear leukocyte β-adrenergic receptor-adenylate cyclase system after long-term catecholamine exposure.