Influence of losartan and enalapril on urinary excretion of 8-isoprostane in experimental nephrotic syndrome.
BACKGROUND
The increased permeability of the glomerular capillary wall in adriamycin nephropathy may be mediated by increased generation of free radicals, possibly also by the non-enzymatic production of isoprostanes induced by oxidative stress. ACE inhibitors and angiotensin II antagonists may reduce proteinuria, perhaps by decreasing intraglomerular pressure and increasing the selective permeabiity of the glomerular capillary wall.


METHODS
We compared the effect of an ACE inhibitor, enalapril, and an angiotensin II antagonist, losartan, on total malodialdehyde in blood 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 partly mitigated by enalapril. However, both losartan and enalapril prevented the adriamycin-induced increase of total MDA in serum, but urinary excretion of 8-isoprostane was increased in nephrotic rats treated by 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-proteinuric rats.


CONCLUSIONS
Proteinuria in the acute phase of adriamycine nephropathy may be dependent on free radical 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 antiproteinuric action of enalapril in this model of nephrotic syndrome.
Tesar
Vladimír
V
Department of Nephrology, 1st Department of Medicine, 1st Medicine Faculty, Charles University, U nemocnice 2, 120 00 Prague 2, Czech Republic.
Zima
Tomás
T
Jirsa
Milan
M
Crkovská
Jirina
J
Stípek
Stanislav
S
Vernerová
Zdenka
Z
Seráková
Markéta
M
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D015237:Dinoprost / Q000031:analogs & derivatives*; D004656:Enalapril / Q000494:pharmacology*; D028441:F2-Isoprostanes / Q000652:urine*; D019808:Losartan / Q000494:pharmacology*; D009404:Nephrotic Syndrome / Q000652:urine*; D051381:Rats
D000806:Angiotensin-Converting Enzyme Inhibitors; D028441:F2-Isoprostanes; D000804:Angiotensin II; C075750:8-epi-prostaglandin F2alpha; D004656:Enalapril; D015237:Dinoprost; D019808:Losartan