Effects of renin-angiotensin blockade on renal function, renal norepinephrine contents and oxidative stress in cyclosporine induced nephrosis rats

Abstract

The objective of this study was to investigate whether of renin-angiotensin blockade improves renal function, renal norepinephrine contents and oxidative stress in cyclosporine (CsA) induced nephrosis rats. Rats were assigned into three groups and were treated as followed; group 1 (control group), receiving vehicle (propylene glycol) 1 ml/k.g./day for 28 days; group 2 (CsA group), receiving CsA 15 mg/kg./day, s.c. for 28 days; group 3 (CsA and losartan group), receiving CsA 15 mg/kg./day, s.c. with administration of losartan 10 mg/k.g./day orally for 28 days. Cyclosporine administration alone elevated mean arterial pressure, deteriorated renal function, as assessed by increased plasma urea nitrogen and decreased GFR. Cyclosporine stimulated renal sympathetic activity as assessed by increased renal norepinephrine content and induced oxidative stress, as indicated by increased renal MDA and decreased concentrations of renal reduced glutathione. No change was noted in renal catalase activity. Losartan, the AT1 receptor antagonist markedly decreased mean arterial pressure, improved renal function, reduced renal norepinephrine contents and reduced level of renal MDA. These results clearly demonstrate that angiotensin II stimulates renal sympathetic activity and induced oxidative stress in CsA induced nephrosis rats. The therapeutic potential of AT1receptor antagonist in ameliorating CsA-induced nephrosis rats is suggested.