(Circulation. 1998;98:2652-2655.)
© 1998 American Heart Association, Inc.
Editorial |
Endothelium as a Therapeutic Target in Heart Failure
From the Department of Cardiology and Angiology, Medizinische Hochschule Hannover, Hannover, Germany.
Correspondence to Helmut Drexler, MD, Abteilung Kardiologie und Angiologie, Medizinische Hochschule Hannover, Carl-Neubergstraße 1, 30625 Hannover, Germany. E-mail drexler.helmut@mh-hannover.de
Key Words: Editorials • nitric oxide • exercise • heart failure
Patients with chronic heart failure are characterized by systemic vasoconstriction and reduced peripheral perfusion, which are thought to contribute to the impaired exercise capacity in this disorder. Whereas an increased sympathetic tone and an activated renin-angiotensin system have been proposed to be involved in the reduced vasodilator capacity in heart failure, the important role of the endothelium in coordinating tissue perfusion has not been recognized until recently. Recent clinical studies have documented impaired endothelium-dependent relaxations of peripheral resistance and conduit arteries in patients with chronic heart failure, most likely due to impaired availability of nitric oxide (NO). On the other hand, the endothelial production of vasoconstricting factors1 such as angiotensin II or endothelin appears to be increased in severe heart failure. Whereas numerous important functions of the endothelium have been recognized in the past, many recent experimental and clinical studies have focused on endothelium-derived NO, probably because one of its main functions, vascular relaxation, can easily be assessed in humans in vivo. NO is a potent endogenous vasodilator and appears to be responsible for the maintenance of basal vascular tone; it is also thought to exert other important effects, such as inhibition/modulation of platelet aggregation, leukocyte adhesion, cell respiration, and apoptosis. The mechanisms of the actions of NO include activation of second messengers such as cGMP, direct effects on redox-sensitive regulatory proteins, and interactions with reactive oxygen species.
Impaired endothelium-dependent vascular relaxation
has been documented in virtually all cardiovascular
disorders and appears to occur early in the course of
cardiovascular
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