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Prevention of structural changes in the heart in hypertension by angiotensin converting enzyme inhibition.

AbstractBACKGROUND:
The long-term effects of hypertension on the heart culminate in congestive heart failure. The underlying causes are contractile impairment due to myocyte loss and reduced compliance due to myocardial fibrosis. Newer strategies in antihypertensive therapy must, therefore, focus on prevention of myocardial damage ('cardioprotection') or, if an abnormality has occurred, on reversal towards normal myocardial structure and function ('cardioreparation').
OBJECTIVE:
To investigate the question of whether angiotensin converting enzyme (ACE) inhibition can influence myocardial remodelling in hypertension to produce cardioprotective and cardioreparative effects.
METHODS AND RESULTS:
Infusion of pathophysiological levels of circulating angiotensin II in rats causes cardiac myocyte necrosis, followed by fibroblast proliferation. This necrosis is not secondary to adrenergic activation or raised blood pressure. Similarly, renovascular hypertension results in cardiac myocyte necrosis, which can be prevented by pretreatment with the ACE inhibitor captopril. In established genetic hypertension in rats, sustained treatment with high-dose lisinopril normalizes the blood pressure, reverses left ventricular hypertrophy, reverses excessive interstitial and perivascular fibrosis (and consequently the impaired compliance), and reverses excessive coronary artery medial thickening (thereby normalizing coronary vascular reserve). With a low dose of lisinopril that does not reduce blood pressure significantly, only the excessive fibrosis is reversed.
CONCLUSION:
ACE inhibition has demonstrated promising myocardial remodelling effects in experimental models of hypertensive heart disease.
AuthorsL B Tan, C Brilla, K T Weber
JournalJournal of hypertension. Supplement : official journal of the International Society of Hypertension (J Hypertens Suppl) Vol. 10 Issue 1 Pg. S31-4 (Apr 1992) ISSN: 0952-1178 [Print] England
PMID1535655 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., Review)
Chemical References
  • Angiotensin-Converting Enzyme Inhibitors
  • Angiotensin II
Topics
  • Angiotensin II (adverse effects)
  • Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
  • Animals
  • Cardiomegaly (prevention & control)
  • Diastole (physiology)
  • Heart Failure (prevention & control)
  • Humans
  • Hypertension (complications, drug therapy)
  • Myocardium (pathology)
  • Rats
  • Rats, Inbred SHR

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