L-Arginine Supplementation Improves Vascular Endothelial Dysfunction Induced by High-Fat Diet in Rats Exposed to Hypoxia

• Published in: Wilderness & environmental medicine 2020-12, Vol.31 (4), p.400-406
• Main Authors: Zhao, Yan-Xia, Tong, Li, Zhang, Guang-Mei, Zhao, Xie-Hui, Sa, Yu-Ping, Liu, Yan, Lu, Dian-Xiang, Ga, Qin, Wu, Ping
• Format: Article
• Language: English
• Subjects: Animals; Aorta - drug effects; Arginine - administration & dosage; Arginine - pharmacology; Body Weight - drug effects; Diet, High-Fat - adverse effects; Dietary Supplements; endothelial nitric oxide synthase; Endothelium, Vascular - drug effects; high altitude; Hypoxia; low density lipoprotein; Male; malondialdehyde; Malondialdehyde - blood; nitric oxide; Nitric Oxide - blood; Random Allocation; Rats; Rats, Sprague-Dawley; RNA, Messenger; Superoxide Dismutase - blood
• ISSN: 1080-6032; 1545-1534
• DOI: 10.1016/j.wem.2020.06.010

Our previous study showed that high-fat diet inhibited the increase in nitric oxide and endothelial nitric oxide synthase expression in the aortic endothelium of rats exposed to hypoxia, and hypoxia plus a high-fat diet led to earlier and more severe vascular endothelial dysfunction (VED) than hypoxia alone. The purpose of the present study was to investigate the effects of L-arginine on high-fat diet–induced VED of rats in hypoxia. Forty male Sprague-Dawley rats were randomly divided into 4 groups and treated with hypoxia (H group), hypoxia plus high-fat diet (H+HFD group), hypoxia plus L-arginine (H+L-Arg group), and hypoxia plus high-fat diet and L-arginine (H+HFD+L-Arg group) for 1 wk. Hypoxia was simulated in a hypobaric chamber with an altitude of 5000 m. Aortic morphology and endothelium-dependent vasorelaxation were used to assess VED. High-fat diet impaired vascular remodeling and reduced endothelium-dependent vasodilator response to acetylcholine in rats exposed to hypoxia, secondary to dysregulation of the nitric oxide pathway. L-arginine supplementation significantly increased plasma nitrates and nitrites and endothelial nitric oxide synthase mRNA levels and improved ultrastructural changes in aortic endothelium and endothelium-dependent vasodilator response. L-arginine prevents aortic ultrastructural changes and reverses VED induced by high-fat diet in rats exposed to hypoxia, which may have implications for VED induced by high-fat diet in high altitude dwellers.