Reactive oxygen species are involved in regulating α1-adrenoceptor-activated vascular smooth muscle contraction

Journal of Biomedical Science

Research

Ming-Ho Tsai¹  Meei Jyh Jiang² 

[1] Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, 70101, Tainan, Taiwan;Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, 70101, Tainan, Taiwan;Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, 70101, Tainan, Taiwan;Cardiovascular Research Center, College of Medicine, National Cheng Kung University, 70101, Tainan, Taiwan;

关键词: Reactive Oxygen Species;    NADPH Oxidase;    Phenylephrine;    Myosin Light Chain Kinase;    MLC20 Phosphorylation;   

DOI  :  10.1186/1423-0127-17-67

 received in 2010-06-15, accepted in 2010-08-23,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundReactive oxygen species (ROS) were shown to mediate aberrant contractility in hypertension, yet the physiological roles of ROS in vascular smooth muscle contraction have remained elusive. This study aimed to examine whether ROS regulate α1-adrenoceptor-activated contraction by altering myosin phosphatase activities.MethodsUsing endothelium-denuded rat tail artery (RTA) strips, effects of anti-oxidants on isometric force, ROS production, phosphorylation of the 20-kDa myosin light chain (MLC20), and myosin phosphatase stimulated by α1-adrenoceptor agonist phenylephrine were examined.ResultsAn antioxidant, N-acetyl-L-cysteine (NAC), and two NADPH oxidase inhibitors, apocynin and VAS2870, dose-dependently inhibited contraction activated by phenylephrine. Phenylephrine stimulated superoxide anion production that was diminished by the pretreatment of apocynin, VAS2870, superoxide scavenger tiron or mitochondria inhibitor rotenone, but not by xanthine oxidase inhibitor allopurinol or cyclooxygenase inhibitor indomethacin. Concurrently, NADPH oxidase activity in RTA homogenates increased within 1 min upon phenylephrine stimulation, sustained for 10 min, and was abolished by the co-treatment with apocynin, but not allopurinol or rotenone. Phenylephrine-induced MLC20 phosphorylation was dose-dependently decreased by apocynin. Furthermore, apocynin inhibited phenylephrine-stimulated RhoA translocation to plasma membrane and phosphorylation of both myosin phosphatase regulatory subunit MYPT1Thr855 and myosin phosphatase inhibitor CPI-17Thr38.ConclusionsROS, probably derived from NADPH oxidase and mitochondria, partially regulate α1-adrenoceptor-activated smooth muscle contraction by altering myosin phosphatase-mediated MLC20 phosphorylation through both RhoA/Rho kinase- and CPI-17-dependent pathways.

【 授权许可】

CC BY   
© Tsai and Jiang; licensee BioMed Central Ltd. 2010