title: Endothelin receptors in augmented vasoconstrictor responses to endothelin-1 in chronic intermittent hypoxia.
abstract: 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. Rats were subjected to CIH (Fi o2 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 in vitro experiments (isometric force measurement), histological analysis, immunohistochemistry and western blotting. Aortas from rats subjected to CIH exhibited marked endothelial dysfunction and increased responsiveness to ET-1. Furthermore, CIH induced increased ET-1 and ETA receptor expression, whereas ETB receptor expression was decreased. Aortic contractile responses to ET-1 were inhibited by the ETA and ETB 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. The results of the present study suggest that increased expression of ETA receptors, which mediate a potent vasoconstrictor response, plays an important role in the pathogenesis of CIH. In addition, decreased endothelial ETB receptor expression, which is associated with the functional decline of endothelium-dependent vasodilation, also contributes to the pathogenesis of CIH. It appears that the ETB receptor-induced buffering of ET-1 responsiveness is mediated via a nitric oxide-dependent mechanism.
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Qiu-Hong
authors.initials: QH
authors.lastname: Guo
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Tian
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Wang
authors.forename: Ai-Ying
authors.initials: AY
authors.lastname: Li
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Ma
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Guo
authors.forename: J Woodrow
authors.initials: JW
authors.lastname: Weiss
authors.forename: En-Sheng
authors.initials: ES
authors.lastname: Ji
authors.forename: Li
authors.initials: L
authors.lastname: Chu
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000235:genetics / Q000378:metabolism*; D044023:Receptor, Endothelin B / Q000235:genetics / Q000378:metabolism*; D014661:Vasoconstriction / Q000235:genetics / Q000502:physiology*; D014664:Vasodilation / Q000235:genetics / Q000502:physiology
chemical_list: D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat