Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The current status and future directions of the pharmacotherapy of dilated cardiomyopathy are reviewed. The Japanese multicenter study on the effect of beta-blockers revealed significant improvement of NYHA functional classification, LV end-diastolic dimension, ejection fraction, and exercise tolerance time in patients with dilated cardiomyopathy. From our study using normal rabbits, metoprolol augmented adenylate cyclase activity without upregulation of the beta-adrenergic receptor number. Carteolol, a beta-adrenergic blocker with intrinsic sympathomimetic action, prevented the development of dilatation and hypertrophy of the heart in the chronic stage following murine encephalomyocarditis (EMC) viral myocarditis. Metoprolol exerted no such effect. Animal experiments indicated that immunosuppressive treatment for inflammatory myocarditis may aggravate the clinical course of the disease. However, immunosuppressive treatment in acute myocarditis should be reevaluated with the use of newly developed antiviral agents. A new synthetic immunoactive peptide FK 565, given before or simultaneously with viral inoculation, proved effective in inhibiting myocardial virus replication and myocardial damage in murine EMC viral myocarditis. Beneficial effects of captopril on survival rate and myocardial injury were demonstrated dose dependently in murine EMC viral myocarditis, even when the treatment was started around the peak of virus replication, namely, on day 4-14 after inoculation. Captopril may be promising for the treatment of acute myocarditis, and hopefully for prevention of the progression from myocarditis to dilated cardiomyopathy.
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PMID:Pharmacotherapy of dilated cardiomyopathy: current status and future directions. 134 97

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.
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PMID:Regulation of cardiac beta-adrenergic receptors by captopril. Implications for congestive heart failure. 254 69