Chronic intermittent hypoxia impairs endothelium-dependent dilation in rat cerebral and skeletal muscle resistance arteries

Abstract

The goal of the present study was to evaluate the effects of relatively short-term chronic intermittent hypoxia (CIH) on endothelial function of resistance vessels in the skeletal muscle and cerebral circulations. Sprague-Dawley rats were exposed to 14 days of CIH (10% fraction of inspired oxygen for 1 min at 4-min intervals, 12 h/day, n = 6). Control rats (n = 6) were housed under normoxic conditions. After 14 days, resistance arteries of the gracilis muscle (GA) and middle cerebral arteries (MCA) were isolated and cannulated with micropipettes, perfused and superfused with physiological salt solution, and equilibrated with 21% O2-5% CO2 in a heated chamber. The arteries were pressurized to 90 mmHg, and vessel diameters were measured via a video micrometer before and after exposure to ACh (10-7-10-4 M), sodium nitroprusside (10-6 M), and acute reduction of Po2 in the perfusate/superfusate (from 140 to 40 mmHg). ACh-induced dilations of GA and MCA from animals exposed to CIH were greatly attenuated, whereas responses to nitroprusside were similar to controls. Dilations of both GA and MCA in response to acute reductions in Po2 were virtually abolished in animals exposed to CIH compared with controls. These findings suggest that exposure to CIH reduces the bioavailability of nitric oxide in the cerebral and skeletal muscle circulations and severely blunts vasodilator responsiveness to acute hypoxia.

Morphological and Functional Alterations of the Ductus Arteriosus in a Chicken Model of Hypoxia-Induced Fetal Growth Retardation

“…In relation to the vascular effects of chronic hypoxia, numerous investigations have examined the involvement of the NO/sGC/cGMP axis in pulmonary and systemic vessels. The majority of these studies report hypoxiainduced endothelial impairment with normal response to NO donors (19,20). However, other authors report alterations in both endothelium-dependent and -independent relaxation after expo- sure to chronic hypoxia (21).…”

Sleep apnoea syndrome in 2011: current concepts and future directions

“…Many biological and pathophysiological changes have been linked to intermittent hypoxia, i.e. alteration in baroreflex activity [91], increase in pulmonary arterial pressure and haematocrit [92], changes in heart structure and function [93], and an alteration in endothelial dependent vasodilation in cerebral and muscular arteries [94]. In addition, an increased response to endothelin (ET)-1 was also demonstrated [89], presumably almost exclusively mediated by ET-A receptors [95].…”

Intermittent hypoxia and sleep-disordered breathing: current concepts and perspectives

“…A variety of biological and pathophysiological changes have also been demonstrated, i.e. altered baroreflex activity [56], increased pulmonary arterial pressure and haematocrit [57], changes in heart structure and function [58], altered endothelium-dependent vasodilation in cerebral and muscular arteries [59], and an increased response to endothelin (ET)-1 [54], presumably mediated almost exclusively by ETA receptors [60]. During IH, both blood pressure (BP) and myocardial changes might be critically dependent upon ET-1.…”