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Transforming growth factor-beta, 20-HETE interaction, and glomerular injury in Dahl salt-sensitive rats.

Abstract
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.
AuthorsAnnette J Dahly-Vernon, Mukut Sharma, Ellen T McCarthy, Virginia J Savin, Steven R Ledbetter, Richard J Roman
JournalHypertension (Hypertension) Vol. 45 Issue 4 Pg. 643-8 (Apr 2005) ISSN: 1524-4563 [Electronic] United States
PMID15723968 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Hydroxyeicosatetraenoic Acids
  • Serum Albumin, Bovine
  • Sodium Chloride, Dietary
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • 20-hydroxy-5,8,11,14-eicosatetraenoic acid
Topics
  • Animals
  • Hydroxyeicosatetraenoic Acids (antagonists & inhibitors)
  • Hypertension (etiology, metabolism)
  • In Vitro Techniques
  • Kidney (metabolism)
  • Kidney Glomerulus (metabolism, pathology)
  • Microscopy, Electron
  • Permeability (drug effects)
  • Rats
  • Rats, Inbred Dahl
  • Rats, Sprague-Dawley
  • Serum Albumin, Bovine (pharmacokinetics)
  • Sodium Chloride, Dietary (administration & dosage, pharmacology)
  • Transforming Growth Factor beta (metabolism, pharmacology)
  • Transforming Growth Factor beta1

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