Effect of tumor necrosis factor alpha inhibition with etanercept on renal functions in L-NAME induced hypertensive rats: insights into the possible mechanisms

Abstract

Many studies suggest the dominant role of the inflammatory cytokine, tumor necrosis factor alpha (TNF-α) in the prognosis of hypertension and end stage renal disease (ESRD). The objective of this study was to investigate the effects of TNF-α inhibition on renal functions in Nω-nitro-L-arginine methyl ester (L-NAME) induced hypertensive rats and the potential underlying mechanisms. Four groups of rats were used in the study for 3 weeks period; normal control group, TNFα inhibitor (etanercept) group, L-NAME-induced hypertensive group and L-NAME + etanercept group. L-NAME group showed elevated systolic and diastolic blood pressure, plasma urea, creatinine, plasma renin activity, angiotensin II, kidney tissue nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, TNFα and malondialdehyde (MDA) together with decreased creatinine clearance rate and renal antioxidants. Treatment with etanercept affords antihypertensive effect and ameliorates L-NAME induced renal impairment by improving renin–angiotensin system (RAS) and NADPH oxidase as well as by attenuating oxidative stress.