Oxidative stress-dependent cyclooxygenase-2-derived prostaglandin F impairs endothelial function in renovascular hypertensive rats

Xiao Yu Tian, Wing Tak Wong, Fung Ping LEUNG, Yang Zhang, Yi Xiang Wang, Hung Kay Lee, Chi Fai Ng, Zhen Yu Chen, Xiaoqiang Yao, Chak Leung Au, Chi Wai Lau, Paul M. Vanhoutte, John P. Cooke, Yu Huang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)

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 (PGF) 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 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. Further, chronic tempol treatment reduced COX-2 and BMP4 upregulation, p38MAPK phosphorylation, and the nitrotyrosine level in RHR renal arteries. Conclusion: 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 plays an important role in mediating endothelial dysfunction in RH. Innovation: The current study, thus, suggests that drugs targeting oxidative stress-dependent COX-2-derived PGF may be useful in the prevention and management of RH.

Original languageEnglish
Pages (from-to)363-373
Number of pages11
JournalAntioxidants and Redox Signaling
Volume16
Issue number4
DOIs
Publication statusPublished - 15 Feb 2012

Scopus Subject Areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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