- 作者: Ming-Ho Tsai; Meei Jyh Jiang
- 作者服務機構: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
Background: Reactive 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.
Methods: Using 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.
Results: An 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.
Conclusions: ROS, 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. - 中文關鍵字: --
- 英文關鍵字: --