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.

Endothelin-1 and ET receptors impair left ventricular function by mediated coronary arteries dysfunction in chronic intermittent hypoxia rats

“…This result was different from our previous research that BQ788 could significantly reduce ET‐1‐mediated contractile responses in aortas and pulmonary arteries (Guo et al. ; Wang et al. ).…”

“…Indeed, these results were consistent with previous studies of ET‐1‐mediated artery and pulmonary dysfunction after CIH exposure (Guo et al. ; Wang et al. ), but few studies has reported ET‐1 and ET receptors changes in coronary arteries after CIH.…”

“…Moreover, previous studies have shown that ET‐1 and ET receptors play a key role in CIH‐induced endothelial dysfunction and augmented vasoconstriction of aortas and pulmonary arteries in rats (Guo et al. ; Wang et al. ).…”

Ameliorative Effect of a Selective Endothelin ETAReceptor Antagonist in Rat Model of L-Methionine-induced Vascular Dementia

“…During endothelial dysfunction, there is increased responsiveness to ET-1 along with increased expression of ET A receptors, which mediate a potent vasoconstrictor response in addition to decreased endothelial ET B receptor expression associated with functional decline of endothelium-dependent vasodilation [49,50]. Hyperhomocysteinemia has been demonstrated to induce endothelial dysfunction by activating ET A receptors and thereby shifting the balance towards enhanced contractility [51].…”

Roles of oestradiol receptor alpha and beta against hypertension and brain mitochondrial dysfunction under intermittent hypoxia in female rats

“…Chronic intermittent hypoxia (CIH) is regularly used in animals to reproduce the recurring drops in arterial oxygen saturation that characterize respiratory patterns of sleep apnoea (SA) patients . CIH induces an elevation of arterial blood pressure that depends on exaggerated activity of peripheral chemoreceptors, leading to high activity of the sympathetic nerves and vascular dysfunction . In the central nervous system, CIH leads to increased levels of oxidative stress and neuronal apoptosis likely underlying cognitive impairments, and support for such findings can also be inferred by recent studies in humans showing reduced cortical thickness in both adult and pediatric SA patients.…”