A 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitor reduces hypertensive nephrosclerosis in stroke-prone spontaneously hypertensive rats

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Abstract
Background Recent studies suggest that 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors (statins) exert their protective effects against cardiovascular diseases independently of their cholesterol-decreasing effects. Objective To clarify the effect of a statin on hypertensive nephrosclerosis. Methods We treated stroke-prone spontaneously hypertensive rats (spSHRs) chronically, starting at the age of 4 weeks, with cerivastatin (2 mg/kg per day by gavage) or vehicle. Physiological parameters, plasma chemistry and urine protein excretion were analysed. At 14 weeks of age, the rats had their kidneys removed for use in assays. Results Compared with vehicle treatment, statin treatment reduced proteinuria and renal injury independently of blood pressure and cholesterol concentrations in spSHRs. Although expression of adhesion molecules and infiltration of inflammatory cells were not different whether or not cerivastatin treatment was used, renal fibrosis was significantly reduced in statin-treated spSHRs. We also found that expression of transforming growth factor-β1 in kidneys was significantly inhibited in statin-treated spSHRs. Conclusion Cerivastatin prevents or retards hypertension-induced renal injury via inhibition of renal fibrosis and proteinuria. These results show the potential of statins as protective tools against proteinuric renal diseases, independent of their cholesterol-decreasing effects.