Regulation of cardiac beta-adrenergic receptors by captopril. Implications for congestive heart failure.
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
A S
AS
Department of Medicine, University of California, San Diego, La Jolla.
Phillips
C
C
Michel
M C
MC
Ziegler
M G
MG
Carter
S M
SM
D000262:Adenylyl Cyclases / Q000032:analysis; D000818:Animals; D002216:Captopril / Q000627:therapeutic use*; D000242:Cyclic AMP / Q000032:analysis; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism; D007545:Isoproterenol / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000032:analysis / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000032:analysis; D009638:Norepinephrine / Q000097:blood; D011869:Radioligand Assay / Q000379:methods; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects*; D012084:Renin-Angiotensin System / Q000187:drug effects; D012508:Sarcolemma / Q000032:analysis / Q000187:drug effects
D011943:Receptors, Adrenergic, beta; D002216:Captopril; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D009638:Norepinephrine