Rosuvastatin improves endothelial function in db/db mice: Role of angiotensin II type 1 receptors and oxidative stress

X. Y. Tian, W. T. Wong, A. Xu, Z. Y. Chen, Y. Lu, L. M. Liu, V. W. Lee, C. W. Lau, X. Yao, Y. Huang

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

BACKGROUND AND PURPOSE HMG-CoA reductase inhibitors, statins, with lipid-reducing properties combat against atherosclerosis and diabetes. The favourable modulation of endothelial function may play a significant role in this effect. The present study aimed to investigate the cellular mechanisms responsible for the therapeutic benefits of rosuvastatin in ameliorating diabetes-associated endothelial dysfunction. EXPERIMENTAL APPROACH Twelve-week-old db/db diabetic mice were treated with rosuvastatin at 20 mg·kg -1·day -1 p.o.for 6 weeks. Isometric force was measured in isolated aortae and renal arteries. Protein expressions including angiotensin II type 1 receptor (AT 1R), NOX4, p22 phox, p67 phox, Rac-1, nitrotyrosine, phospho-ERK1/2 and phospho-p38 were determined by Western blotting, while reactive oxygen species (ROS) accumulation in the vascular wall was evaluated by dihydroethidium fluorescence and lucigenin assay. KEY RESULTS Rosuvastatin treatment of db/db mice reversed the impaired ACh-induced endothelium-dependent dilatations in both renal arteries and aortae and prevented the exaggerated contractions to angiotensin II and phenylephrine in db/db mouse renal arteries and aortae. Rosuvastatin reduced the elevated expressions of AT 1R, p22 phox and p67 phox, NOX4, Rac1, nitrotyrosine and phosphorylation of ERK1/2 and p38 MAPK and inhibited ROS production in aortae from db/db mice. CONCLUSIONS AND IMPLICATIONS The vasoprotective effects of rosuvastatin are attributed to an increase in NO bioavailability, which is probably achieved by its inhibition of ROS production from the AT 1R-NAD(P)H oxidase cascade.

Original languageEnglish (US)
Pages (from-to)598-606
Number of pages9
JournalBritish Journal of Pharmacology
Volume164
Issue number2 B
DOIs
StatePublished - Sep 2011

Keywords

  • diabetes
  • endothelial function
  • oxidative stress
  • statin
  • vasodilatation

ASJC Scopus subject areas

  • Pharmacology

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