Angiotensin II blockade decreases TGF-β1 and matrix proteins in cyclosporine nephropathy

摘要: Angiotensin II (Ang II) is implicated in fibrosis but the precise mechanism of this effect remains unclear. In a model chronic cyclosporine (CsA) nephropathy, we previously showed that TGF-beta1 plays role CsA-induced tubulointerstitial and arteriolopathy by stimulating extracellular matrix (ECM) protein synthesis inhibiting ECM degradation through increasing plasminogen activator inhibitor (PAI)-1. We hypothesized Ang contributes to inducing TGF-beta1. Salt-depleted rats were given placebo, CsA alone, + nilvadipine, hydralazine/hydrochlorthiazide, losartan (AT1 receptor antagonist) or enalapril converting enzyme inhibitor) sacrificed at 7 28 days. All treated groups achieved similar blood pressures glomerular filtration rates. The lesion nephropathy was ameliorated concomitant therapy with days, phenomenon not observed other treatment groups. Similarly, blockade resulted decreased expression PAI-1 Northern ELISA. proteins directly influenced TGF-beta blockade. These results suggest independent renal hemodynamics mediated, least partly, induction expression.