Endothelial Dysfunction in Heart Failure: Mechanisms and Therapeutic Approaches
Abstract:Endothelial dysfunction contributes to the development of impaired coronary and systemic perfusion as well as reduced exercise capacity in patients with congestive heart failure (CHF). Thereby endothelial dysfunction is assumed to have a fundamental impact on morbidity and potential mortality in this disease. Reduced bioavailability of nitric oxide (NO) and abundant formation of reactive oxygen species (ROS) within the vascular wall are the key determinants in endothelial dysfunction. The resulting imbalance between NO and ROS mainly results from neurohumoral activation associated with CHF. The excessive activation of the renin-angiotensinaldosterone and endothelin systems plays a pivotal role. Treatment with ACE inhibitors, angiotensin-, aldosterone-, and endothelin-antagonists has been shown to beneficially modulate endothelial dysfunction in CHF. Furthermore, antioxidants, L-arginine, cofactors of endothelial NO-synthase, and exercise training positively modulate endothelial function.
This article reviews the current knowledge of the pathophysiological events contributing to endothelial dysfunction in CHF as well as several treatment options to reverse those changes.
Document Type: Review Article
Affiliations: Medizinische Universitätsklinik, Josef-Schneider-Str. 2, D-97080 Würzburg, Germany.
Publication date: April 1, 2004
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- Vascular disease is the commonest cause of death in Westernized countries and its incidence is on the increase in developing countries. It follows that considerable research is directed at establishing effective treatment for acute vascular events. Long-term treatment has also received considerable attention (e.g. for symptomatic relief). Furthermore, effective prevention, whether primary or secondary, is backed by the findings of several landmark trials.
Vascular disease is a complex field with primary care physicians and nurse practitioners as well as several specialties involved. The latter include cardiology, vascular and cardio thoracic surgery, general medicine, radiology, clinical pharmacology and neurology (stroke units). Current Vascular Pharmacology will publish reviews to update all those concerned with the treatment of vascular disease. For example, reviews commenting on recently published trials or new drugs will be included. In addition to clinically relevant topics we will consider 'research-based' reviews dealing with future developments and potential drug targets. Therefore, another function of Current Vascular Pharmacology is to bridge the gap between clinical practice and ongoing research.
Debates will also be encouraged in the correspondence section of this journal.