Endothelin receptors in augmented vasoconstrictor responses to endothelin-1 in chronic intermittent hypoxia
Endothelin receptors in augmented vasoconstrictor responses to endothelin-1 in chronic intermittent hypoxia
复制标题
慢性间歇性缺氧中内皮素受体增强内皮素-1 的血管收缩反应
DOI：
10.1111/1440-1681.12109
复制
发表时间：
2013-07-01
影响因子：
2.9
通讯作者：
Chu, Li
中科院分区：
文献类型：
--
作者：
Guo, Qiu-Hong;Tian, Yi-Long;Chu, Li
慢性间歇性低氧(CIH)是阻塞性睡眠呼吸暂停患者发生心血管疾病的重要原因。许多研究表明循环内皮素(ET)-1水平升高与脑出血之间存在关联。本研究的目的是确定ET受体在脑出血动物模型主动脉功能改变中的作用。大鼠给予9%FiO2处理1min，每2min重复一次，每天8h，每周7d，共3周。3周后处死大鼠，取主动脉用于体外实验(等长力测量)、组织学分析、免疫组织化学和Western blotting。脑出血大鼠的主动脉表现出明显的内皮功能障碍和对ET-1的反应性增加。此外，CIH诱导ET-1和ETA受体表达增加，而ETB受体表达降低。ETA和ETB受体拮抗剂BQ-123和BQ-788分别抑制ET-1引起的主动脉收缩反应。CIH大鼠的主动脉对乙酰胆碱的舒缩反应明显减弱，而CIH对硝普钠所致的主动脉反应无明显影响。本研究结果提示，介导强大的血管收缩反应的ETA受体表达增加在脑出血的发病机制中起重要作用。此外，内皮ETB受体表达减少与内皮依赖性血管扩张功能下降有关，也参与了CIH的发病机制。ETB受体对ET-1反应性的缓冲作用似乎是通过一氧化氮依赖机制来实现的。
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 1min, repeated every 2min for 8h/day, 7days/week) for 3weeks. After 3weeks, 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.