期刊
JOURNAL OF HYPERTENSION
卷 27, 期 3, 页码 599-605出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/HJH.0b013e32831ef369
关键词
angiotensin II; cell adhesion; ICAM-1; inflammation; iNOS; renal protection; rosuvastatin
资金
- AstraZeneca Germany
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 NOS expression in small vessels, infiltrating cells, afferent arterioles, and glomeruli of dTGR. Immunoreactivity was stronger in cortex than medulla. Rosuvastatin markedly reduced the NOS 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. J Hypertens 27:599-605 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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