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22 February 2002

Influence of losartan and enalapril on urinary excretion of 8-isoprostane in experimental nephrotic syndrome.

Vladimír Tesar, Tomás Zima, Milan Jirsa, Jirina Crkovská, Stanislav Stípek, Zdenka Vernerová, Markéta Seráková

Med Sci Monit 2002; 8(2): BR69-74 :: ID: 420944

Abstract

BACKGROUND: The increased permeability of the glomerular capillary wallin adriamycin nephropathy may be mediated by increased generation of free radicals, possibly also bythe non-enzymatic production of isoprostanes induced by oxidative stress. ACE inhibitors and angiotensinII antagonists may reduce proteinuria, perhaps by decreasing intraglomerular pressure and increasingthe selective permeabiity of the glomerular capillary wall. MATERIAL/METHODS: We compared the effectof an ACE inhibitor, enalapril, and an angiotensin II antagonist, losartan, on total malodialdehyde inblood and the urinary excretion of certain eicosanoids and their metabolites (TxB(2), 6-keto-PGF(1alpha),bicyclo-PGE(2) and 8-isoprostane) in experimental adriamycin-induced nephrotic syndrome in rats. RESULTS:Increased proteinuria in adriamycin-treated rats was not prevented by losartan, but tended to be partlymitigated by enalapril. However, both losartan and enalapril prevented the adriamycin-induced increaseof total MDA in serum, but urinary excretion of 8-isoprostane was increased in nephrotic rats treatedby losartan compared to controls. The enalapril-induced increase in urinary excretion of bicyclo-PGE(2)was possibly mediated by kinins. Proteinuria positively correlated with urinary excretion of 8-isoprostane,and proteinuric rats also had a significantly higher urinary excretion of 8-isoprostane than non-proteinuricrats. CONCLUSIONS: Proteinuria in the acute phase of adriamycine nephropathy may be dependent on freeradical generation and the formation of 8-isoprostane. The mild antiproteinuric effect of enalapril,but not losartan, may suggest the contributory role of the inhibition of kinin degradation in the antiproteinuricaction of enalapril in this model of nephrotic syndrome.

Keywords: Angiotensin-Converting Enzyme Inhibitors, Comparative Study, Dinoprost, enalapril, F2-Isoprostanes, Losartan, nephrotic syndrome, Research Support, Non-U.S. Gov

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750