Endothelial dysfunction and atherosclerosis: Endothelin receptor antagonists as novel therapeutics

被引：41

作者：

Barton M. ^{[1
]}

机构：

[1] Cardiology, Department of Medicine, University Hospital Zürich, CH-8091 Zürich

来源：

Current Hypertension Reports | 2000年 / 2卷 / 1期

基金：

美国国家卫生研究院;

关键词：

Nitric Oxide; Vascular Smooth Muscle Cell; Receptor Blockade; Fatty Streak Formation; Experimental Hypercholesterolemia;

D O I：

10.1007/s11906-000-0064-5

中图分类号：

学科分类号：

摘要：

Atherosclerosis, a chronic systemic disease of the vascu-lature with an inflammatory component, is the primary cause of cardiovascular morbidity and mortality in industrialized countries [1]. It is associated with the impairment of endothelium-dependent relaxation in the coronary, systemic circulation due to decreased bioavailability of nitric oxide, and increased release oxygen-derived free radicals, thus promoting vasoconstriction, leukocyte adhesion, thrombosis, inflammation, and cell proliferation [2]. Expression of endothelin (ET)-1, a 21-amino acid peptide and major isoform of the endothelin peptide family, is produced by endothelial, vascular smooth muscle cells, and macrophages and acts through Gi-protein-coupled ETA and ETB receptors. Endothelin-1 increases in hyper-cholesterolemia and atherosclerosis in humans and experimental animals. This paper reviews current experimental and clinical evidence for the involvement of ET-1 in athero-genesis. Furthermore, the effects of ET receptor blockade on experimental hypercholesterolemia and atherosclerosis will be discussed. As chronic endothelin blockade inhibits fatty streak formation and improves vascular function in experimental hypercholesterolemia, hypertension, and heart failure, and as it restores nitric oxide (NO)-mediated endothelial function and reduces atheroma formation in animals with atherosclerosis, endothelin receptor blockade may therefore offer a novel approach for the treatment of atherosclerosis and its vascular complications.

引用

页码：84 / 91

页数：7

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