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

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

Volume: 11 Issue: 13

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

Affiliation:

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

Abstract: 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.

Cite this article as:

Lin Chih-Lung, Jeng Y. Arco, Howng Shen-Long and Kwan Aij-Lie, Endothelin and Subarachnoid Hemorrhage-Induced Cerebral Vasospasm: Pathogenesis and Treatment, Current Medicinal Chemistry 2004; 11 (13) . https://dx.doi.org/10.2174/0929867043364919