Endothelin receptors in augmented vasoconstrictor responses to endothelin-1 in chronic intermittent hypoxia

Summary 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 rol...

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Bibliographic Details
Published in:Clinical and experimental pharmacology & physiology 2013-07, Vol.40 (7), p.449-457
Main 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
Format: Article
Language:English
Subjects:
Animals
aorta
Aorta - metabolism
Aorta - physiopathology
chronic intermittent hypoxia
Disease Models, Animal
Endothelin A Receptor Antagonists
Endothelin B Receptor Antagonists
endothelin receptors
endothelin-1
Endothelin-1 - genetics
Endothelin-1 - metabolism
Endothelium, Vascular - metabolism
Endothelium, Vascular - physiopathology
Hypoxia - genetics
Hypoxia - metabolism
Hypoxia - physiopathology
Male
Nitric Oxide - genetics
Nitric Oxide - metabolism
Nitric Oxide Synthase Type III - genetics
Nitric Oxide Synthase Type III - metabolism
Rats
Rats, Sprague-Dawley
Receptor, Endothelin A - genetics
Receptor, Endothelin A - metabolism
Receptor, Endothelin B - genetics
Receptor, Endothelin B - metabolism
Vasoconstriction - genetics
Vasoconstriction - physiology
Vasodilation - genetics
Vasodilation - physiology
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Summary:Summary 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 (Fio2 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.
ISSN:0305-1870
1440-1681
DOI:10.1111/1440-1681.12109