Influence of Losartan and Enalapril on Urinary 8-isoprostane Excretion inExperimental Nephrotic Syndrome

Overview

Background.
Increased permeability of glomerular capillary wall in adriamycin nephropathy may be mediatedby increased generation of free radicals and possibly also by the non-enzymatic production of isoprostanes inducedby oxidative stress. ACE inhibitors may reduce proteinuria, possibly due to the decrease of intraglomerular pressureand increased permselectivity of the glomerular capillary wall. These effects may be partly mediated by the inhibitionof the degradation of kinins. It is not clear if newly available angiotensin II antagonists have the same antiproteinuricand renoprotective effects.Methods and Results. We compared the effect of an ACE inhibitor (enalapril, 0.4 mg/kg bw i.p. daily for 3 weeks)and angiotensin II antagonist (losartan, 2 mg/kg bw in the same way) on experimental nephrotic syndrome inducedin rats by the administration of adriamycin (5 mg/kg bw i.v. in a single dose). To elucidate the potential differencesbetween these two drugs we also measured total malondialdehyde in blood and urinary excretion some eicosanoidsand their metabolites (TxB2, 6-keto-PGF1alfa, bicyclo-PGE2 and 8-isoprostane).Proteinuria increased in adriamycin treated rats after 3 weeks from 0.18 ± 0.01 to 0.44 ± 0.14 g/mmol creat, p

Key words:
losartan, enalapril, adriamycin, nephropathy, malondialdehyde, lipoperoxidation, eicosanoids, iso-prostans.