This study examined the role of
transforming growth factor-beta (
TGF-beta) in altering the glomerular permeability to
albumin (P(alb)) during
hypertension development in Dahl
salt-sensitive (Dahl S) rats and whether
TGF-beta acts by inhibiting the glomerular production of
20-HETE. The results indicate that the renal expression of
TGF-beta doubles in Dahl S rats fed a high-
salt diet for 7 days, and this is associated with a marked rise in P(alb) from 0.19+/-0.04 to 0.75+/-0.01 and changes in the ultrastructure of the glomerular filtration barrier. Chronic treatment of Dahl S rats with a
TGF-beta neutralizing antibody prevented the increase in P(alb) and preserved the structure of glomerular capillaries. It had no effect on the rise in blood pressure produced by the high-
salt diet. In other studies, preincubation of glomeruli isolated from Sprague Dawley rats with
TGF-beta1 (10 ng/mL) for 15 minutes increased P(alb) from 0.01+/-0.01 to 0.60+/-0.02. This was associated with inhibition of the glomerular production of
20-HETE from 221+/-11 to 3.4+/-0.5 mug per 30 minutes per milligram of
protein. Pretreatment of Sprague Dawley glomeruli with a stable analog of
20-HETE, 20-hydroxyeicosa-5(Z), 14(Z)-dienoic
acid, reduced baseline P(alb) and opposed the effects of
TGF-beta to increase P(alb). These studies indicate that upregulation of the glomerular formation of
TGF-beta may contribute to the development of
proteinuria and glomerular injury early in
hypertension development in Dahl S rats by increasing P(alb) through inhibition of the glomerular production of
20-HETE.