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European Heart Journal 1990 11(Supplement D):11-16; doi:10.1093/eurheartj/11.suppl_D.11
Copyright © 1990 by the European Society of Cardiology.
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© 1990 The European Society of Cardiology

The role of tissue renin-angiotensin systems in hypertension and effects of chronic converting-enzyme inhibition

C. Keuneke, R. Yacullo, R. Metzger, T. Hellmann, J. Peters and D. Ganten

German Institute for High Blood Pressure Research and Department of Pharmacology, University of Heidelberg Heidelberg, F.R.G.

Address for correspondence: Detlev Ganten, M.D., Ph.D., German Institute for High Blood Pressure Research and Department of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, D-6900 Heidelberg 1, F.R.G.

When inhibitors of the renin-angiotensin system (RAS) were initially developed, they were believed to act as antihypertensive agents mainly under pathophysiological conditions, in which an elevated plasma RAS contributed to the elevation and maintenance of high blood pressure (BP). However, evidence has accumulated from studies in hypertensive patients, as well as in animals, indicating that BP could be lowered by converting-enzyme inhibitors (CEIs) independently of- whether or not the plasma RAS was stimulated. Several other effects had to be considered. It war thus discovered that converting enzyme (CE) is identical with the bradykinin-degrading enzyme, kininase II, and CEIs can therefore potentiate the vasodepressor effects of bradykinin and thereby interact with the prostaglandin system. Actions of CEIs possibly unrelated to inhibition of angiotensin and kininase also need to be considered.

The actions of CEIs at the tissue level (brain, heart, blood vessels, kidney, adrenal gland) and their interference with the autonomic nervous system through central and peripheral actions may under certain conditions be more important than their inhibition of the circulating hormonal plasma angiotensin II. Recent clinical and experimental studies and new insights in the molecular biology of the RAS, especially gene expression of renin and angiotensinogen in tissues of the cardiovascular system, support this view. We have found that chronic CE inhibition with substances such as captopril, quinapril and lisinopril specifically affects angiotensinogen mRNA levels in cardiovascular tissues, and has marked effects on left ventricular hypertrophy, possibly through an action on cardiac angiotensin. These findings have consequences not only for the understanding of pharmacokinetics and pharmacodynamics of CEIs but also for their practical therapeutic use.

Key Words: Renin-angiotensin system • cardiac hypertrophy • converting-enzyme inhibitors • angiotensinogen • gene expression • mRNA drug effects


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