Myocardial response to stress in cardiac hypertrophy and heart failure: effect of antihypertensive drugs.
The myocardium's response to increased stress or load is not stereotyped. Differences have been observed in the heart's molecular composition and performance characteristics when exposed to stress. Myosin isoforms gradually change during development of hypertrophy, whereas collagen levels change only during the chronic phase of hypertrophy. Cardiac hypertrophy can regress if treated with antihypertensive drugs, but the myocardium of the post-hypertrophic heart no longer has the same composition as it did before hypertrophy. In rat studies of the effects of antihypertensive drugs on cardiac functional reserve, captopril showed a regression of hypertrophy associated with a lower baseline stroke volume and, after dobutamine stress, a dose-dependent rise in stroke volume. In untreated rates captopril showed no change in stroke volume. In hydralazine-treated rats, there was no change in reserve after dobutamine stress, whereas propranolol treatment resulted in partial regression and a slight change in stroke volume. Overall, our data suggests that development of hypertension and hypertrophy plays a role in changes in the molecular structure of the myocardium, especially during the chronic phase of hypertrophy and heart failure. This complex process cannot be explained by one factor but involves a combination of factors. Identification of each factor would be of importance for the development of appropriate therapeutic agents.
Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Foundation, Ohio 44195, USA. sens@cesmtp.ccf.org
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D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002303:Cardiac Output, Low / Q000503:physiopathology*; D006332:Cardiomegaly / Q000503:physiopathology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism; D018450:Disease Progression; D004280:Dobutamine / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D009206:Myocardium / Q000201:enzymology; D009218:Myosins / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013314:Stress, Mechanical
D000959:Antihypertensive Agents; D002316:Cardiotonic Agents; D020033:Protein Isoforms; D004280:Dobutamine; D003094:Collagen; D009218:Myosins