title: Oxidative stress-dependent cyclooxygenase-2-derived prostaglandin f(2α) impairs endothelial function in renovascular hypertensive rats.
abstract: Abstract   Aims: The role of endothelium-derived contracting factors (EDCFs) in regulating renovascular function is yet to be elucidated in renovascular hypertension (RH). The current study investigated whether oxidative stress-dependent cyclooxygenase (COX)-2-derived prostaglandin F(2α) (PGF(2α)) impairs endothelial function in renal arteries of renovascular hypertensive rats (RHR).
  
  
  RESULTS
  Renal hypertension was induced in rats by renal artery stenosis of both kidneys using the 2-kidney 2-clip model. Acute treatment with reactive oxygen species (ROS) scavengers, COX-2 inhibitors, and thromboxane-prostanoid receptor antagonists, but not COX-1 inhibitors, improved endothelium-dependent relaxations and eliminated endothelium-dependent contractions in RHR renal arteries. Five weeks of treatment with celecoxib or tempol reduced blood pressure, increased renal blood flow, and restored endothelial function in RHRs. Increased ROS production in RHR arteries was inhibited by ROS scavengers, but unaffected by COX-2 inhibitors; whereas increased PGF(2α) release was reduced by both ROS scavengers and COX-2 inhibitors. ROS also induced COX-2-dependent contraction in RHR renal arteries, which was accompanied by the release of COX-2-derived PGF(2α). Further, chronic tempol treatment reduced COX-2 and BMP4 upregulation, p38MAPK phosphorylation, and the nitrotyrosine level in RHR renal arteries.
  
  
  CONCLUSIONS
  These findings demonstrate the functional importance of oxidative stress, which serves as an initiator of increased COX-2 activity, and that COX-2-derived PGF(2α) plays an important role in mediating endothelial dysfunction in RH.
  
  
  METHODS
  The current study, thus, suggests that drugs targeting oxidative stress-dependent COX-2-derived PGF(2α) may be useful in the prevention and management of RH. Antioxid. Redox Signal. 16, 363-373.
authors.affiliation: Institute of Vascular Medicine, Li Ka Shing Institute of Health Sciences, School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Xiao Yu
authors.initials: XY
authors.lastname: Tian
authors.forename: Wing Tak
authors.initials: WT
authors.lastname: Wong
authors.forename: Fung Ping
authors.initials: FP
authors.lastname: Leung
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yi-Xiang
authors.initials: YX
authors.lastname: Wang
authors.forename: Hung Kay
authors.initials: HK
authors.lastname: Lee
authors.forename: Chi Fai
authors.initials: CF
authors.lastname: Ng
authors.forename: Zhen Yu
authors.initials: ZY
authors.lastname: Chen
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Yao
authors.forename: Chak Leung
authors.initials: CL
authors.lastname: Au
authors.forename: Chi Wai
authors.initials: CW
authors.lastname: Lau
authors.forename: Paul M
authors.initials: PM
authors.lastname: Vanhoutte
authors.forename: John P
authors.initials: JP
authors.lastname: Cooke
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015237:Dinoprost / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D006978:Hypertension, Renovascular / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015237:Dinoprost; D051546:Cyclooxygenase 2