Interaction of angiotensin II and TGF-beta 1 in the rat remnant kidney.
An interaction between angiotensin (Ang) II and transforming growth factor (TGF)-beta 1 is gaining increasing recognition. Ang II has been implicated in the progression of renal disease, and TGF-beta 1 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-beta 1 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-beta 1 mRNA (194 +/- 64 versus 411 +/- 101 optical density units, P < 0.05, losartan versus control) and TGF-beta 1 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-beta 1 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-beta 1. 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-beta 1.
Junaid
A
A
University of Manitoba, Winnipeg, Canada.
Rosenberg
M E
ME
Hostetter
T H
TH
D000804:Angiotensin II / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D046508:Culture Techniques; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007668:Kidney / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009392:Nephrectomy; D009929:Organ Size / Q000187:drug effects; D012313:RNA / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000378:metabolism*
D000959:Antihypertensive Agents; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D012313:RNA; D019808:Losartan