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Rosuvastatin protects against angiotensin II-induced renal injury in a dose-dependent fashion

Item Type:Article
Title:Rosuvastatin protects against angiotensin II-induced renal injury in a dose-dependent fashion
Creators Name:Park, J.K. and Mervaala, E.M. and Mueller, D.N. and Menne, J. and Fiebeler, A. and Luft, F.C. and Haller, H.
Abstract:OBJECTIVE: We showed earlier that statin treatment ameliorates target-organ injury in a transgenic model of angiotensin (Ang) II-induced hypertension. We now test the hypothesis that rosuvastatin (1, 10, and 50 mg/kg/day) influences leukocyte adhesion and infiltration, prevents induction of inducible nitric oxide synthase (iNOS), and ameliorates target-organ damage in a dose-dependent fashion. METHODS: We treated rats harboring the human renin and human angiotensinogen genes (dTGR) from week 4 to 8 (n = 20 per group). Untreated dTGR developed severe hypertension, cardiac hypertrophy, and renal damage, with a 100-fold increased albuminuria and focal cortical necrosis. Mortality of untreated dTGR at age 8 weeks was 59%. RESULTS: Rosuvastatin treatment decreased mortality dose-dependently. Blood pressure was not affected. Albuminuria was reduced dose-dependently. Interstitial adhesion molecule (ICAM)-1 expression was markedly reduced by rosuvastatin, as were neutrophil and monocyte infiltration. Immunohistochemistry showed an increased endothelial and medial iNOS expression in small vessels, infiltrating cells, afferent arterioles, and glomeruli of dTGR. Immunoreactivity was stronger in cortex than medulla. Rosuvastatin markedly reduced the iNOS expression in both cortex and medulla. Finally, matrix protein (type IV collagen, fibronectin) expression was also dose- dependently reduced by rosuvastatin. CONCLUSION: Our findings indicate that rosuvastatin dose- dependently ameliorates angiotensin II-induced-organ damage and almost completely prevents inflammation at the highest dose. The data implicate 3-hydroxy-3-methylglutaryl coenzyme A function in signaling events leading to target-organ damage.
Keywords:Angiotensin II, Cell Adhesion, ICAM-1, Inflammation, iNOS, Renal Protection, Rosuvastatin, Animals, Rats
Source:Journal of Hypertension
ISSN:0263-6352
Publisher:Lippincott Williams & Wilkins (U.S.A.)
Volume:27
Number:3
Page Range:599-605
Date:March 2009
Official Publication:https://doi.org/10.1097/HJH.0b013e32831ef369
PubMed:View item in PubMed

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