HOLMER, SR and RIEGGER, GAJ (1995) ROLE OF THE CARDIAC RENIN-ANGIOTENSIN SYSTEM IN HYPERTENSIVE HEART-DISEASE. HERZ, 20 (5). pp. 322-329. ISSN 0340-9937, 1615-6692
Full text not available from this repository.Abstract
Chronic mechanical stress of the heart by arterial hypertension is a primary cause of left ventricular hypertrophy. The cardiac renin-angiotensin system is often found activated in conditions of increased afterload or mechanical stress of myocytes. Cardiac expression of angiotensinogen and angiotensin-converting enzyme (ACE) is increased resulting in elevated cardiac angiotensin II formation, This has been demonstrated in stretched cardiac myocytes in vitro as well as in animal models of pressure overload hypertrophy (supravalvular aortic stenosis and spontaneously hypertensive rats) and in human pressure overload hypertrophy (aortic stenosis). Functional consequences of elevated angiotensin II levels may be vasoconstriction of the coronary vasculature and a deterioration of diastolic function of the hypertrophied heart. Local formation of angiotensin II may also have proliferative effects on cardiac myocytes and connective tissue cells. Angiotensin II may, thus. be an important factor causing development and progression of left ventricular hypertrophy by itself. Blockade of the renin-angiotensin system has been found to be an effective treatment of hypertensive heart disease, probably better than any other antihypertensive medication. Regression of left ventricular hypertrophy has been acchieved by blockade of the angiotensin II pathway either by administration of an angiotensin-converting enzyme inhibitor or an angiotensin II type 1-receptor blocker. The animal model of supravalvular aortic stenosis has been used to show beneficial effects of blockade of the renin-angiotensin system on hypertrophy and survival. In this rat model regression of left ventricular hypertrophy by ACE-inhibition or angiotensin II type 1-receptor blockade could be demonstrated by serial echocardiographic analyses while afterload of the left ventricle was still elevated. Functional benefits of blockade of the renin-angiotensin system include a marked improvement of diastolic function. In addition to adaptive changes of the renin-angiotensin system in pressure overload hypertrophy genetically determined activity of this system seems to be a risk factor for left ventricular hypertrophy per se. Genetic variants of the renin-angiotensin system may determine individual activity of the system. The insertion/deletion (IID) polymorphism of the angiotensin-converting enzyme has been associated with plasma activities of the enzyme in a way that homozygous DD individuals show higher activity. Population based studies in Europe and Japan showed that this genotype may be associated with an elevated risk of left ventricular hypertrophy particularly in normotensive individuals. Thus, variants of the angiotensin-converting enzyme gene or a gene nearby may be a risk factor for left ventricular hypertrophy per se. Interestingly, this IID-polymorphism has also been associated with other cardiovascular disorders like myocardial infarction, diabetic vasculopathy, and carotid wall thickening. Future studies are required to elucidate molecular mechanisms by which genetic variants of the renin-angiotensin system confer increased risk of such cardiovascular diseases. Furthermore, genetic analysis may allow to identify individuals at high risk and may, thus, have major influence on treatment strategies of individuals with hypertensive heart disease in the future.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LEFT-VENTRICULAR HYPERTROPHY; CONVERTING ENZYME-INHIBITION; DELETION POLYMORPHISM; RAT-HEART; REGRESSION; CAPTOPRIL; RISK; MASS; CARDIOMYOPATHY; EXPRESSION; |
| Depositing User: | Dr. Gernot Deinzer |
| Last Modified: | 19 Oct 2022 08:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/52288 |
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