title: Protective effects of rosuvastatin in experimental renal failure rats via improved endothelial function.
abstract: Rosuvastatin is a statin (3-hydroxy-3-methylglutaryl coenzyme-A [HMG-CoA] reductase inhibitor) that also serves as an endothelial dysfunction salvager in many disease models. Endothelial dysfunction is assumed to play a pivotal role in the process of chronic renal failure. The authors tested rosuvastatin on a rat model of renal failure with hypertension. Renal failure was induced by 5/6 nephrectomy (Nx). Fisher rats were divided into four groups: sham (n = 10), sham + rosuvastatin (n = 10), Nx (n = 9), and Nx + rosuvastatin (n =10). After 4 weeks, the authors determined renal function, lipid profile, and urine albumin excretion, investigated small renal arteries for endothelium function in response to acetylcholine by perfused juxtamedullary nephron technique, and detected intrarenal inflammatory cytokine expression by real-time reverse transcription polymerase chain reaction. 5/6 Nx significantly increased blood urea nitrogen, serum creatinine, and systolic/diastolic blood pressure, and severe albuminuria developed. The deterioration of renal function, hypertension, and albuminuria were almost normalized by rosuvastatin therapy; in addition, rosuvastatin prevented intrarenal inflammatory cytokine expression and the impaired response to acetylcholine of the renal endothelium. Microscopically, rosuvastatin significantly inhibited the development of progressing renal fibrosis, preserved glomerular structure and tubular integrity, and significantly reduced the degree of tubular atrophy and interstitial fibrosis. In conclusion, HMG-CoA reductase inhibitor rosuvastatin can ameliorate markers of endothelium dysfunction and offers a significant protective effect against the development of renal failure caused by 5/6 Nx in rats. Rosuvastatin might, therefore, represent a novel therapeutic agent for chronic kidney disease.
authors.affiliation: Department of Nursing, Tongji University Institute of Medical Science, Shanghai, People's Republic of China.
authors.forename: Yong-zhen
authors.initials: YZ
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Yi-ming
authors.initials: YM
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Kang
authors.forename: Ping-zhi
authors.initials: PZ
authors.lastname: Chen
authors.forename: Ze-feng
authors.initials: ZF
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Feng
authors.forename: Jun-hua
authors.initials: JH
authors.lastname: Zheng
mesh_terms: D000818:Animals; D005464:Fluorobenzenes / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D011743:Pyrimidines / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D060888:Real-Time Polymerase Chain Reaction; D051437:Renal Insufficiency / Q000188:drug therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium