Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 164, Issue 2B, Pages 598-606Publisher
WILEY
DOI: 10.1111/j.1476-5381.2011.01416.x
Keywords
statin; diabetes; endothelial function; oxidative stress; vasodilatation
Categories
Funding
- Research Council of Hong Kong [HKU2/07C, HKU4/CRF10]
- CUHK Li Ka Shing Institute of Health Sciences
- [4653/08 M]
- [466110]
Ask authors/readers for more resources
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(1)R), 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 AT1R, 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(1)R-NAD(P) H oxidase cascade.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available