Effects of the Renin-Angiotensin Blockade on Renal Functions, Renal Norepinephrine Contents and Oxidative Stress in Cyclosporine Induced Nephrosis Rats

Abstract

The experiment was conducted to investigate the effects of renin-angiotensin blockade on renal function, renal norepinephrine (NE) contents and renal oxidative stress in Cyclosporine A (CsA) induced renal impairment in rats. Rats were assigned into three groups; group 1 (control group), receiving vehicle (propylene glycol) 1 ml/kg./day, subcutaneously (s/c). for 28 days; group 2 (CsA group), receiving CsA 15 mg/kg/day, s/c for 28 days; group 3 (CsA and losartan (LST) group), receiving CsA 15 mg/kg./day, s/c with the administration
of LST 10 mg/k.g./day orally for 28 days. The results showed that CsA administration alone elevated mean arterial pressure (MAP), reduced renal function, as assessed by increased plasma urea nitrogen and decreased
glomerular filtration rate. CsA stimulated renal sympathetic activity as assessed by increased renal NE content and induced oxidative stress, as indicated by increased renal malondialdehyde (MDA) and decreased concentrations of renal reduced glutathione (GSH). Losartan, the angiotensin type 1 (AT1) receptor antagonist markedly decreased MAP, improved renal function, reduced renal NE content and reduced renal MDA. It is concluded that enhanced renal sympathetic activity and oxidative stress by CsA were mediated by angiotensin II. Blocking the renin-angiotensin system can ameliorate the renal impairment caused by CsA.