Angiotensin-Converting Enzyme Inhibition Attenuates Proteinuria and Renal TGF-[beta]1 mRNA Expression in Rats with Chronic Renal Disease

• Published in: Pharmacology Vol. 57; no. 1; p. 20
• Main Authors: Ali, Shujath M, Laping, Nicholas J, Fredrickson, Todd A, Contino, Lisa C, Olson, Barbara A, Anderson, Karen, Brooks, David P
• Format: Journal Article
• Language: English
• Published: Basel S. Karger AG 01.07.1998
• ISSN: 0031-7012; 1423-0313
• DOI: 10.1159/000028222

Evidence suggests that transforming growth factor beta 1 (TGF-β1), a multifunctional cytokine, induces renal extracellular matrix production and glomerular hypertrophy. The aim of the present study was to investigate the effect of captopril on the expression of TGF-β1 mRNA in a rat model of chronic renal failure: five-sixths nephrectomy. Chronic renal disease was induced by removal of the right kidney and ligation of three blood vessels supplying the left kidney. Sham-operated animals were used as controls. RNA was extracted from the viable remnant kidney of rats 1 day and 1 and 2 weeks following five-sixths nephrectomy and from the kidneys of rats who underwent sham sugery. TGF-β1 mRNA was induced within 24 h of partial nephrectomy, similar to that reported for early-onset genes. Subsequently, TGF-β1 mRNA expression continued to increase over the next 2-4 weeks. The upregulation of TGF-β1 correlated with the degree of proteinuria. Both the increase in TGF-β1 mRNA and proteinuria were abrogated by captopril treatment. In addition, no change in expression of ALK-5 or type II TGF-β receptors following five-sixths nephrectomy was observed. These data suggest that captopril may protect against development of glomerulosclerosis and proteinuria by reducing TGF-β1 expression and hence matrix production. [PUBLICATION ABSTRACT]