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Therefore, the present study was designed to examine the early (beginning 2 days before NS induction) and late (beginning 2 wk after NS induction) effects of eplerenone and enalapril, alone or combined, on proteinuria and nephrin\/podocin abundance in rats with adriamycin-induced NS. Adriamycin caused a significant increase in daily protein excretion (U<jats:sub>pr<\/jats:sub>V; from 26.96 \u00b1 3.43 to 958.57 \u00b1 56.7 mg\/day, P &lt; 0.001) and cumulative proteinuria [from 900.33 \u00b1 135.5 to 22,490.62 \u00b1 931.26 mg ( P &lt; 0.001)] during 6 wk. Early treatment with enalapril significantly decreased U<jats:sub>pr<\/jats:sub>V from 958.6 \u00b1 56.7 to 600.31 \u00b1 65.13 mg\/day ( P &lt; 0.001) and cumulative proteinuria to 12,842.37 \u00b1 1,798.17 mg\/6 wk ( P &lt; 0.001). Similarly, early treatment with eplerenone produced a profound antiproteinuric effect: U<jats:sub>pr<\/jats:sub>V decreased from 958.57 \u00b1 56.7 to 593.38 \u00b1 21.83 mg\/day, P &lt; 0.001, and cumulative proteinuria to 16,601.84 \u00b1 1,334.31 mg\/6 wk; P &lt; 0.001. An additive effect was obtained when enalapril and eplerenone were combined: U<jats:sub>pr<\/jats:sub>V decreased from 958.57 \u00b1 56.69 to 424.17 \u00b1 38.54 mg\/day, P &lt; 0.001, and cumulative protein excretion declined to 10,252.88 \u00b1 1,011.3 mg\/6 wk, P &lt; 0.001. These antiproteinuric effects were associated with substantial preservation of glomerular nephrin and podocin. In contrast, late treatment with either enalapril or eplerenone alone or combined mildly decreased U<jats:sub>pr<\/jats:sub>V and cumulative proteinuria. Thus pretreatment with eplerenone or enalapril is effective in reducing daily and cumulative protein excretion and preservation of nephrin\/podocin. More profound antiproteinuric effects were obtained when enalapril and eplerenone were combined.<\/jats:p>","DOI":"10.1152\/ajprenal.00524.2007","type":"journal-article","created":{"date-parts":[[2007,12,20]],"date-time":"2007-12-20T01:34:48Z","timestamp":1198114488000},"page":"F628-F637","source":"Crossref","is-referenced-by-count":23,"title":["Eplerenone potentiates the antiproteinuric effects of enalapril in experimental nephrotic 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