Copyright © 1995 by the European Society of Cardiology.
© 1995 The European Society of Cardiology
Effects of angiotensin receptor antagonists in heart failure: Clinical and experimental aspects
Department of Internal Medicine, Cardiology/Angiology, Virchow-Klinikum, Humboldt University Berlin, and German Heart Institute Berlin, Germany
Correspondence: PD Dr. Regitz-Zagrosek DHZB, Augustenburger Platz I. 13353 Berlin, Germany
In addition to inhibition of the circulating renin-angiotensin system, specific inhibition of the cardiac effects of angiotensin II (Ang II) represents an important therapeutic goal in the treatment of clinical heart failure. Subtype 1-specific Ang II receptor (AT1) antagonists have been developed to overcome potential limitations of angiotensin converting enzyme inhibitors, e.g. insufficient control of tissue Ang II production and bradykinin-related side effects. Clinical studies have demonstrated beneficial effects of AT antagonists. In a single-dose study, the AT1 antagonist losartan decreased the mean arterial pressure and pulmonary arterial pressure while increasing the cardiac index. Effects were dose dependent. Haemodynamic effects were greater with higher doses, but neurohormonal counter-regulation probably also increased, leading to relatively high levels of circulating Ang II with the 150-mg dose. A decrease in plasma levels of noradrenaline, atrial natriuretic factor, and aldosterone reached partial signnificance. Admistration of multiple doses of losartan for 12 weeks also led to favourable haemodynamic and clinical results. Arterial blood pressure, pulmonary capillary wedge pressure, and systemic vascular resistance decreased The neurohormonal effects of 12 weeks' administration of AT1 antagonists consisted in a decrease in plasma aldosterone concentrations. Whereas AT antagonists may counteract the effects of Ang II on the vasculature, and therefore are effective vasodilators, their direct myocardial effects are less clear. The subtype AT2 which represents the dominant receptor in both healthy and failing human myocardium, is not blocked by AT1, inhibition. Angiotensin receptors on isolated human cardiac fibroblasts stimulate cellular proliferation via a yet undetermined receptor subtype. AT1, antagonists exert beneficial haemodynamic and neurohormonal effects in human heart failure. Their direct myocardial effects require further investigation.
Key Words: Angiotensin II receptors • AT1 antagonists • angiotensin receptor regulation
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