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  • Title: eNOS gene delivery prevents hypertension and reduces renal failure and injury in rats with reduced renal mass.
    Author: Savard S, Lavoie P, Villeneuve C, Agharazii M, Lebel M, Larivière R.
    Journal: Nephrol Dial Transplant; 2012 Jun; 27(6):2182-90. PubMed ID: 22121231.
    Abstract:
    BACKGROUND: Impaired nitric oxide (NO) release in chronic renal failure has been implicated in the pathogenesis of hypertension and the progression of renal insufficiency. We investigated whether gene delivery of the endothelial NO synthase (eNOS) improves NO release and reduces blood pressure and renal failure and injury in rats with reduced renal mass. METHODS: Renal failure was induced by renal artery branches ligation. Two weeks later, rats with renal failure were divided into three groups and received an intravenous injection of the vehicle or the adenovirus that expresses eNOS or β-galactosidase (β-gal). Systolic blood pressure, renal parameters and histopathology were assessed at Week 4 after gene delivery. RESULTS: At the end of the study, systolic blood pressures, serum creatinine, proteinuria, urinary endothelin-1 (ET-1) excretion and renal cortex ET-1 levels were increased, whereas plasma and urine NO(2)/NO(3) were reduced in renal failure rats as compared to normal controls. Renal injury comprised blood vessel media hypertrophy, focal and segmental glomerular sclerosis, tubular atrophy and interstitial fibrosis. Gene delivery of eNOS, but not β-gal, prevented an increase in systolic blood pressure and proteinuria, and a reduction in plasma and urine NO(2)/NO(3). eNOS gene delivery also reduced a rise in serum creatinine, urinary ET-1 excretion and renal cortex ET-1 levels, and the renal vascular, glomerular and tubular injury. CONCLUSION: This study indicates that eNOS gene delivery in rats with renal failure improves NO release, which likely prevents the aggravation of hypertension and slows down the progression of renal failure and injury.
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