Captopril treatment up-regulated cardiac beta 1-adrenergic receptors and attenuated the down-regulation of cardiac beta-receptors induced by long-term isoproterenol exposure in guinea pigs.
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 beta-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 beta 1- but not mononuclear leukocyte beta 2-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 beta-adrenergic receptors. Concomitant treatment with captopril attenuated alterations of heart weight, plasma norepinephrine levels, and cardiac beta-receptor density and function. In contrast to its cardiac effects, captopril treatment did not diminish the down-regulation of mononuclear leukocyte beta 2-adrenergic receptors by isoproterenol. Our data suggest that captopril may resensitize the cardiac but not the mononuclear leukocyte beta-adrenergic receptor-adenylate cyclase system after long-term catecholamine exposure.
Maisel et al. (Fri,) conducted a other in Congestive heart failure (implications for). Captopril, isoproterenol, or both was evaluated on Cardiac beta-adrenergic receptor density and function, and adenylate cyclase activity. Captopril treatment up-regulated cardiac beta 1-adrenergic receptors and attenuated the down-regulation of cardiac beta-receptors induced by long-term isoproterenol exposure in guinea pigs.