INTERACTION OF ANGIOTENSIN-II AND TGF-BETA-1 IN THE RAT REMNANT KIDNEY

An interaction between angiotensin (Ang) II and transforming growth fa ctor (TGF)-beta 1 is gaining increasing recognition. Ang II has been i mplicated in the progression of renal disease, and TGF-beta 1 is a pot ent fibrosis-promoting cytokine. We sought to determine whether the be neficial effects of renin-angiotensin system blockade on remnant kidne y function were associated with a reduction in renal TGF-beta 1 in thi s model of chronic renal failure. After subtotal renal ablation, rats fed a 40% protein diet and treated with losartan not only had a reduct ion in systolic BP (96 +/- 8 versus 130 +/- 8 mmHg, P < 0.05, losartan versus control) and urinary protein excretion (4 +/- 5 versus 23 +/- 20 g/d, P < 0.05, losartan versus control), but also exhibited a reduc tion in renal TGF-beta 1 mRNA (194 +/- 64 versus 411 +/- 101 optical d ensity units, P < 0.05, losartan versus control) and TGF-beta 1 protei n levels (9.8 +/- 2.5 versus 18.6 +/-: 5.8 ng/g of renal tissue, P < 0 .05, losartan versus control). The elevation of TGF-beta 1 in the remn ant kidney was most pronounced in the scar region (22.9 +/- 13.1 versu s 5.8 +/- 3.7 ng/g, P < 0.05, scar versus nonscar). A combination of r eserpine, hydralazine, and hydrochlorothiazide, although effective in lowering systemic BP in this model of chronic renal failure, was not a ssociated with a reduction in proteinuria or TGF-beta 1. We conclude t hat in this model of progressive renal injury, Ang II antagonism may e xert a beneficial effect in part by its negative influence on TGF-beta 1.