Advanced glycation end-product levels in subtotally nephrectomized rats: Beneficial effects of angiotensin II receptor 1 antagonist losartan

The angiotensin II receptor 1 antagonist losartan (L) inhibited the advance d glycated end-products (AGEs) induced expression of transforming growth fa ctor beta(1) in in vitro experiments performed on renal tubuloepithelial ce lls. To test the pathophysiological importance of these findings, the possi ble link between serum AGEs levels and angiotensin system was investigated in the model of normotensive subtotally nephrectomized rats (4/6-NX). Conce ntration of AGEs in serum of placebo administered 4/6-NX rats (n=7, 1.09+/- 0.09 U/I) increased slightly in comparison with sham-operated healthy contr ols (CTRL, n = 8, 0.94+/-0.10 U/I, p <0.02) as measured by competitive ELIS A. Treatment of 4/6-NX rats with L over 12 weeks ameliorated the rise in se rum AGEs concentration (1.00+/-0.12 U/I, n=15 p<0.005) almost to the level observed for CTRL. This effect was further corroborated by the observation, that the impaired renal excretion of AGEs in 4/6-NX-placebo rats (0.07+/-0 .02 U/mu mol creatinine) was significantly restored by L (0.09+/-0.02 U/mu mol creatinine, p <0.009) and resembled that of the CTRL (0.10+/-0.03 U/mu mol creatinine). Administration of L to 4/6-NX rats significantly improved renal function as evaluated by a smaller rise in serum creatinine and urea concentration. In spite of the improvement in renal function, there were no differences in concentrations of transforming growth factor p, in serum an d in urine among the two groups. These effects were independent of blood pr essure. Our data give first evidence, that long-term treatment with angiote nsin II receptor 1 antagonist may exert salutary effects on AGEs levels in the rat remnant kidney model, probably due to improved renal function. Copy right (C) 2000 S. Karger AG, Basel.