Angiotensin II type 1 receptor-dependent oxidative stress mediates endothelial dysfunction in type 2 diabetic mice

Wing Tak Wong, Xiao Yu Tian, Aimin Xu, Chi Fai Ng, Hung Kay Lee, Zhen Yu Chen, Chak Leung Au, Xiaoqiang Yao, Yu Huang

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

The mechanisms underlying the effect of the renin-angiotensin-aldosterone system (RAAS) inhibition on endothelial dysfunction in type 2 diabetes are incompletely understood. This study explored a causal relationship between RAAS activation and oxidative stress involved in diabetes-associated endothelial dysfunction. Daily oral administration of valsartan or enalapril at 10mg/kg/day to db/db mice for 6 weeks reversed the blunted acetylcholine-induced endothelium-dependent dilatations, suppressed the upregulated expression of angiotensin II type 1 receptor (AT1R) and NAD(P)H oxidase subunits (p22phox and p47phox), and reduced reactive oxygen species (ROS) production. Acute exposure to AT1R blocker losartan restored the impaired endothelium-dependent dilatations in aortas of db/db mice and also in renal arteries of diabetic patients (fasting plasma glucose level ≥7.0 mmol/l). Similar observations were also made with apocynin, diphenyliodonium, or tempol treatment in db/db mouse aortas. DHE fluorescence revealed an overproduction of ROS in db/db aortas which was sensitive to inhibition by losartan or ROS scavengers. Losartan also prevented the impairment of endothelium-dependent dilatations under hyperglycemic conditions that were accompanied by high ROS production. The present study has identified an initiative role of AT1R activation in mediating endothelial dysfunction of arteries from db/db mice and diabetic patients.

Original languageEnglish (US)
Pages (from-to)757-768
Number of pages12
JournalAntioxidants and Redox Signaling
Volume13
Issue number6
DOIs
StatePublished - Sep 15 2010

ASJC Scopus subject areas

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

Fingerprint

Dive into the research topics of 'Angiotensin II type 1 receptor-dependent oxidative stress mediates endothelial dysfunction in type 2 diabetic mice'. Together they form a unique fingerprint.

Cite this