Effect of pravastatin on nephroprotection in deoxycorticosterone acetate–salt hypertensive rats


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Abstract

ObjectiveEndothelin-1 (ET-1) has been implicated in the pathogenesis of renal impairment. The current study was undertaken to assess the effect of pravastatin on the progression of renal impairment in deoxycorticosterone acetate (DOCA)–salt hypertensive rats.MethodsFour weeks after the start of DOCA–salt treatment and uninephrectomization, male Wistar rats were treated with one of the following therapies for 8 weeks: vehicle; a nonselective endothelin receptor antagonist bosentan; pravastatin; or hydralazine.ResultsTreatment with bosentan or pravastatin was associated with reductions in blood pressure and renal medullary hydroxyproline content, and improvement in glomerular filtration rate, urinary protein excretion, macrophage infiltration, tubular injury, and vascular injury, but not glomerulosclerosis. The renal medullary ET-1 protein levels and preproET-1 mRNA assessed by western blotting and real-time quantitative reverse transcription-PCR were significantly decreased (both P < 0.001) in the pravastatin-treated rats compared with vehicle, which was also confirmed by immunohistochemical analysis. However, there were no significant differences of ET-1 levels in the renal cortex among the DOCA–salt groups. The nephroprotective effects of pravastatin were not associated with its antihypertensive action because hydralazine despite reducing blood pressure failed to improve renal function and disorder.ConclusionThese results suggest a crucial role of renal endothelin system in the pathogenesis of renal functional and structural alterations in the DOCA–salt hypertensive rats. Pravastatin administration ameliorates the impairment of renal function and structures by attenuating medullary ET-1 expression, independent of systemic blood pressure.

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