Aldosterone participates in the pathophysiology of several models of progressive chronic renal disease. Because of the causal connection between transforming growth factor-β1 (TGF-β) and scarring in many such models, we hypothesized that aldosterone could evoke TGF-β in the kidney. Aldosterone infusion for 3 days in otherwise normal rats caused a more than twofold increase in TGF-β excretion without changes in systolic pressure or evidence of kidney damage. Concurrent treatment with amiloride did not alter this effect, indicating that aldosterone's stimulation of TGF-β was independent of its regulation of sodium or potassium transport. However, concurrent treatment with spironolactone did block the increase in TGF-β, indicating that the effect depends on the mineralocorticoid receptor. Renal mRNA for serum glucocorticoid kinase rose, but no change in TGF-β message occurred, suggesting posttranscriptional enhancement of renal TGF-β. In summary, aldosterone provokes renal TGF-β, and this action may contribute to aldosterone's fibrotic propensity.
- Transforming growth factor-β