Endothelin and Subarachnoid Hemorrhage-Induced Cerebral Vasospasm: Pathogenesis and Treatment

Author(s): Chih-Lung Lin, Arco Y. Jeng, Shen-Long Howng, Aij-Lie Kwan

Journal Name: Current Medicinal Chemistry

Volume 11 , Issue 13 , 2004

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Endothelin (ET)-mediated vasoconstriction has been implicated in the pathophysiology of various disorders, e.g. hypertension, chronic heart failure, acute renal failure, pulmonary hypertension, and subarachnoid hemorrhage (SAH)-induced cerebral vasospasm. The potential involvement of ETs in cerebral vasospasm following SAH has triggered considerable interest in designing therapeutic strategies to inhibit biological effects of ET. Major approaches include: (a) reducing the levels of circulating ET- 1 by the the specific anti- ET- 1 antibodies, (b) antagonizing the ET receptors, and (c) suppressing the biosynthesis of ET- 1. To date, numerous antagonists of ETA and / or ETB receptors have been discovered, and some are under clinical evaluation. Inhibitors of endothelin-converting enzymes (ECEs), which catalyze the biosynthesis of ET-1, have also been synthesized. Two types of ECE-1 inhibitors have been evaluated in various animal disease models: dual ECE-1 / neutral endopeptidase 24.11 (NEP) inhibitors and selective ECE-1 inhibitors. In this article, the effects of ET receptor antagonists and ECE-1 inhibitors on the prevention and reversal of SAHinduced cerebral vasospasm in preclinical animal models are reviewed.

Keywords: endothelin, endothelin receptor antagonists, endothelin-converting enzyme inhibitors, subarachnoid hemorrhage, cerebral vasospasm

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Article Details

Year: 2004
Page: [1779 - 1791]
Pages: 13
DOI: 10.2174/0929867043364919
Price: $65

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