Enalapril prevents tubulointerstitial lesions by hyperoxaluria

Hyperoxaluria is a recognized cause of tubulointerstitial lesions, and this could contribute to development of hypertension and chronic renal failure. Enalapril has been effective against the progression of tubulointerstitial lesions in various animal models. The aim of the present study was to eval uate the usefulness of enalapril on the tubulointerstitial damage produced by oxalates. Two-month-old male Sprague-Dawley rats were separated into 4 g roups, control with tap water (G1), hyperoxaluric (G2), hyperoxaluric+enala pril (G3), enalapril (G4), for 4 weeks. G2 and G3 rats were given 1% ethyle neglycol (ETG, precursor for oxalates), and G3 and G4 rats were given enala pril 20 mg/L in drinking water. At the end of the study, we evaluated renal tubulointerstitial lesions by a semiquantitative score. Urine albumin excr etion, serum and urine nitric oxide production, tubulointerstitial immunost aining by alpha-smooth muscle actin, transforming growth factor-beta(1), an d collagen type III were measured. Rats belonging to the hyperoxaluric grou p treated with enalapril (G3) showed fewer tubulointerstitial lesions (1.3/-0.2 versus 3+/-0.2; P<0.01), lower urine albumin excretion (8+/-2 mg/d ve rsus 25+/-2 mg/d; P<0.01), less percentage of alpha-smooth muscle actin in renal interstitium (2+/-0.4% versus 13.5+/-2.4%; P<0.01), less percentage o f transforming growth factor-beta(1) in tubulointerstitial area (3.3+/-1% v ersus 13.3+/-2.1%; P<0.01), less percentage of collagen type III interstiti al deposition (0.7+/-0.5% versus 7+/-2.6%; P<0.01), and increased NO produc tion in serum as well as urine (both P<0.01), when compared with the hypero xaluric group not treated with enalapril (G2). Considering these data, we b elieve that enalapril, by several mechanisms of action, could provide an im portant benefit in the prevention of inflammatory response, transforming gr owth factor-beta(1) tubulointerstitial production, collagen type III inters titial deposition, and finally, the progressive tubulointerstitial fibrosis caused by oxalates.