NADPH Oxidase Accounts for Changes in Cerebrovascular Redox Status in Hindlimb Unweighting Rats

• Published in: Biomedical and environmental sciences Vol. 28; no. 11; pp. 799 - 807
• Main Authors: PENG, Liang, RAN, Hai Hong, ZHANG, Ying, ZHAO, Yu, FAN, Yong Yan, PENG, Li, ZHANG, Ran, CAO, Feng
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2015
• Subjects: Acetophenones; Animals; Cerebral Arteries - metabolism; Glutathione Peroxidase - metabolism; Glutathione peroxidase-1; Hindlimb Suspension; Male; Manganese superoxide dismutase; Membrane Glycoproteins - metabolism; Mesenteric Arteries - metabolism; Microgravity; mRNA水平; Myocytes, Smooth Muscle - metabolism; NADPH oxidase; NADPH Oxidase 2; NADPH Oxidase 4; NADPH Oxidases - antagonists & inhibitors; NADPH Oxidases - metabolism; NADPH氧化酶; Oxidative stress; Rats, Sprague-Dawley; Reactive Oxygen Species; Superoxide Dismutase - metabolism; 大鼠脑; 模拟失重; 氧化还原状态; 脑血管; 血管平滑肌细胞; 锰超氧化物歧化酶; Oxidative stress; Microgravity; NADPH oxidase; Manganese superoxide dismutase; Glutathione peroxidase-1
• ISSN: 0895-3988; 2214-0190
• DOI: 10.1016/S0895-3988(15)30110-0

Objective The roles of cerebrovascular oxidative stress in vascular functional remodeling have been described in hindlimb-unweighting （HU） rats. However, the underlying mechanism remains to be established. Methods We investigated the generation of vascular reactive oxygen species （ROS）, Nox2/Nox4 protein and mRNA levels, NADPH oxidase activity, and manganese superoxide dismutase （MnSOD） and glutathione peroxidase-1 （GPx-1） mRNA levels in cerebral and mesenteric smooth muscle cells （VSMCs） of HU rats. Results ROS production increased in cerebral but not in mesenteric VSMCs of HU rats compared with those in control rats. Nox2 and Nox4 protein and mRNA levels were increased significantly but MnSOD/GPx-1 mRNA levels decreased in HU rat cerebral arteries but not in mesenteric arteries. NADPH oxidases were activated significantly more in cerebral but not in mesenteric arteries of HU rats. NADPH oxidase inhibition with apocynin attenuated cerebrovascular ROS production and partially restored Nox2/Nox4 protein and mRNA levels, NADPH oxidase activity, and MnSOD/GPx-1 mRNA levels in cerebral VSMCs of HU rats. Conclusion These results suggest that vascular NADPH oxidases regulate cerebrovascular redox status and participate in vascular oxidative stress injury during simulated microgravity.