Effect of aldosterone on renal transforming growth factor-beta.
Aldosterone participates in the pathophysiology of several models of progressive chronic renal disease. Because of the causal connection between transforming growth factor-beta(1) (TGF-beta) and scarring in many such models, we hypothesized that aldosterone could evoke TGF-beta in the kidney. Aldosterone infusion for 3 days in otherwise normal rats caused a more than twofold increase in TGF-beta 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-beta was independent of its regulation of sodium or potassium transport. However, concurrent treatment with spironolactone did block the increase in TGF-beta, indicating that the effect depends on the mineralocorticoid receptor. Renal mRNA for serum glucocorticoid kinase rose, but no change in TGF-beta message occurred, suggesting posttranscriptional enhancement of renal TGF-beta. In summary, aldosterone provokes renal TGF-beta, and this action may contribute to aldosterone's fibrotic propensity.
Juknevicius
Irmantas
I
National Kidney Disease Education Program, National Institutes of Health, National Institute of Diabetes, Digestive, and Kidney Diseases, 6707 Democracy Blvd, Rm. 645, Bethesda, MD 20892, USA.
Segal
Yoav
Y
Kren
Stefan
S
Lee
Rutha
R
Hostetter
Thomas H
TH
D000450:Aldosterone / Q000008:administration & dosage / Q000494:pharmacology* / Q000652:urine; D000803:Angiotensin I / Q000096:biosynthesis; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004343:Drug Implants; D005786:Gene Expression Regulation / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D023282:Nuclease Protection Assays; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D013268:Stimulation, Chemical; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics / Q000652:urine; D014882:Water-Electrolyte Balance / Q000187:drug effects
D004343:Drug Implants; D016212:Transforming Growth Factor beta; D000450:Aldosterone; D000803:Angiotensin I; D012083:Renin