Endothelin receptors in augmented vasoconstrictor responses to endothelin‐1 in chronic intermittent hypoxia. (21st June 2013)

• Record Type: Journal Article
• Authors: Guo, Qiu‐Hong; Tian, Yi‐Long; Wang, Zhuo; Li, Ai‐Ying; Ma, Zhi‐Hong; Guo, Ya‐Jing; Weiss, J Woodrow; Ji, En‐Sheng; Chu, Li
• Is Part Of: Clinical and experimental pharmacology and physiology. Volume 40:Number 7(2013:Jul.)
• Page Start: 449
• Page End: 457
• Publication Date: 2013-06-21
• Subjects: Clinical pharmacology -- Periodicals; Pharmacology, Experimental -- Periodicals; Physiology, Experimental -- Periodicals; Physiology, Pathological -- Periodicals; 615.1
• DOI: 10.1111/1440-1681.12109
• Languages: English
• ISSNs: 0305-1870

Abstract

<abstract abstract-type="main" id="cep12109-abs-0001"> <title>Summary</title> <p> <list id="cep12109-list-0001" list-type="order"> <list-item> <p>Chronic intermittent hypoxia (CIH) contributes to the development of cardiovascular diseases in patients with obstructive sleep apnoea. Many studies have shown an association between increased circulating endothelin (ET)‐1 levels and CIH. The aim of the present study was to determine the role of ET receptors in altered aortic function in an animal model of CIH.</p> </list-item> <list-item> <p>Rats were subjected to CIH (<italic>F</italic><sub>i</sub><sc>o</sc><sub>2</sub> 9% for 1 min, repeated every 2 min for 8 h/day, 7 days/week) for 3 weeks. After 3 weeks, the rats were killed and their aortas retrieved for use in <italic>in vitro</italic> experiments (isometric force measurement), histological analysis, immunohistochemistry and western blotting.</p> </list-item> <list-item> <p>Aortas from rats subjected to CIH exhibited marked endothelial dysfunction and increased responsiveness to ET‐1. Furthermore, CIH induced increased ET‐1 and ET<sub>A</sub> receptor expression, whereas ET<sub>B</sub> receptor expression was decreased. Aortic contractile responses to ET‐1 were inhibited by the ET<sub>A</sub> and ET<sub>B</sub> receptor antagonists BQ‐123 and BQ‐788, respectively. Acetylcholine‐induced relaxation responses were significantly attenuated in aortas from rats subjected to CIH, whereas CIH had no significant effect on aortic responses to sodium nitroprusside.</p> </list-item> <list-item> <p>The results of the present study suggest that increased expression of ET<sub>A</sub> receptors, which mediate a potent vasoconstrictor response, plays an important role in the pathogenesis of CIH. In addition, decreased endothelial ET<sub>B</sub> receptor expression, which is associated with the functional decline of endothelium‐dependent vasodilation, also contributes to the pathogenesis of CIH. It appears that the ET<sub>B</sub> receptor‐induced buffering of ET‐1 responsiveness is mediated via a nitric oxide‐dependent mechanism.</p> </list-item> </list> </p> </abstract>