Chronic intermittent hypobaric hypoxia protects vascular endothelium by ameliorating autophagy in metabolic syndrome rats.

ABSTRACT

AIMS: The study aimed to investigate the protective effect of chronic intermittent hypobaric hypoxia (CIHH) on endothelium function and relaxation of mesenteric artery in metabolism syndrome (MS) rats. MAIN METHODS: Male adult Sprague-Dawley rats were randomly divided into control (CON), CIHH (treated with 28-days hypobaric hypoxia simulating an altitude of 5000 m, 6 h daily), MS (induced by high fat diet and 10% fructose water feeding), and MS + CIHH groups. Body weight, systolic arterial pressure, blood biochemical and the endothelium dependent relaxation (EDR) of mesenteric arteries were measured. The expression of phosphor-endothelial nitric oxide synthase (p-eNOS), endoplasmic reticulum (ER) stress-related proteins and autophagy-related proteins in mesenteric arteries was assayed. KEY FINDINGS: The MS rats displayed hypertension, obesity, metabolic abnormity and insulin resistance, EDR was attenuated, p-eNOS expression was down-regulated, the expressions of ER stress-related proteins were up-regulated, and autophagy dysfunction occurred. All aforementioned abnormalities in MS rats were ameliorated in MS + CIHH rats. Furthermore, the improvement of CIHH on EDR and p-eNOS was cancelled by the ER stress inducer, and the autophagy inhibitor. SIGNIFICANCE: In conclusion CIHH protects endothelium function and enhances relaxation in mesenteric arteries of MS rats through improving autophagy function, reducing ER stress and up-regulating p-eNOS.