TY - JOUR
T1 - Interaction of angiotensin II and TGF-β1 in the rat remnant kidney
AU - Junaid, Asad
AU - Hostetter, Thomas H.
AU - Rosenberg, Mark E.
PY - 1997/11
Y1 - 1997/11
N2 - An interaction between angiotensin (Ang) II and transforming growth factor (TGF)-β1 is gaining increasing recognition. Ang II has been implicated in the progression of renal disease, and TGF-β1 is a potent fibrosis-promoting cytokine. We sought to determine whether the beneficial effects of renin-angiotensin system blockade on remnant kidney function were associated with a reduction in renal TGF-β1 in this model of chronic renal failure. After subtotal renal ablation, rats fed a 40% protein diet and treated with losartan not only had a reduction 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 reduction in renal TGF-β1 mRNA (194 ± 64 versus 411 ± 101 optical density units, P < 0.05, losartan versus control) and TGF-β1 protein 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-β1 in the remnant kidney was most pronounced in the scar region (22.9 ± 13.1 versus 5.8 ± 3.7 ng/g, P < 0.05, scar versus nonscar). A combination of reserpine, hydralazine, and hydrochlorothiazide, although effective in lowering systemic BP in this model of chronic renal failure, was not associated with a reduction in proteinuria or TGF-β1. We conclude that in this model of progressive renal injury, Ang II antagonism may exert a beneficial effect in part by its negative influence on TGF-β1.
AB - An interaction between angiotensin (Ang) II and transforming growth factor (TGF)-β1 is gaining increasing recognition. Ang II has been implicated in the progression of renal disease, and TGF-β1 is a potent fibrosis-promoting cytokine. We sought to determine whether the beneficial effects of renin-angiotensin system blockade on remnant kidney function were associated with a reduction in renal TGF-β1 in this model of chronic renal failure. After subtotal renal ablation, rats fed a 40% protein diet and treated with losartan not only had a reduction 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 reduction in renal TGF-β1 mRNA (194 ± 64 versus 411 ± 101 optical density units, P < 0.05, losartan versus control) and TGF-β1 protein 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-β1 in the remnant kidney was most pronounced in the scar region (22.9 ± 13.1 versus 5.8 ± 3.7 ng/g, P < 0.05, scar versus nonscar). A combination of reserpine, hydralazine, and hydrochlorothiazide, although effective in lowering systemic BP in this model of chronic renal failure, was not associated with a reduction in proteinuria or TGF-β1. We conclude that in this model of progressive renal injury, Ang II antagonism may exert a beneficial effect in part by its negative influence on TGF-β1.
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U2 - 10.1681/asn.v8111732
DO - 10.1681/asn.v8111732
M3 - Article
C2 - 9355076
AN - SCOPUS:0030724927
SN - 1046-6673
VL - 8
SP - 1732
EP - 1738
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 11
ER -