This Article Full Text Full Text (PDF) All Versions of this Article: 45/4/643    most recent 01.HYP.0000153791.89776.43v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dahly-Vernon, A. J. Articles by Roman, R. J. Search for Related Content PubMed PubMed Citation Articles by Dahly-Vernon, A. J. Articles by Roman, R. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information High Blood Pressure Related Collections Lipids Animal models of human disease

(Hypertension. 2005;45:643.)
© 2005 American Heart Association, Inc.

Harry Goldblatt Award

Transforming Growth Factor-ß, 20-HETE Interaction, and Glomerular Injury in Dahl Salt-Sensitive Rats

Annette J. Dahly-Vernon; Mukut Sharma; Ellen T. McCarthy; Virginia J. Savin; Steven R. Ledbetter; Richard J. Roman

From the Departments of Physiology, Medicine, and Kidney Disease Center (A.J.D.-V., M.S., E.T.M., V.J.S., R.J.R.), Medical College of Wisconsin, Milwaukee; and Genzyme Corporation (S.R.L.), Framingham, Mass.

Correspondence to Richard J. Roman, Medical College of Wisconsin, Department of Physiology, 8701 Watertown Plank Rd, Milwaukee, WI 53226-4801. E-mail rroman{at}mcw.edu

This study examined the role of transforming growth factor-ß (TGF-ß) in altering the glomerular permeability to albumin (P_alb) during hypertension development in Dahl salt-sensitive (Dahl S) rats and whether TGF-ß acts by inhibiting the glomerular production of 20-HETE. The results indicate that the renal expression of TGF-ß 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-ß 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-ß1 (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 µg 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-ß to increase P_alb. These studies indicate that upregulation of the glomerular formation of TGF-ß 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.

Key Words: transforming growth factors • kidney • hypertension, renal

This article has been cited by other articles:

				K. Inoue, K. Sodhi, N. Puri, K. H. Gotlinger, J. Cao, R. Rezzani, J. R. Falck, N. G. Abraham, and M. Laniado-Schwartzman Endothelial-specific CYP4A2 overexpression leads to renal injury and hypertension via increased production of 20-HETE Am J Physiol Renal Physiol, October 1, 2009; 297(4): F875 - F884. [Abstract] [Full Text] [PDF]

				D. S. Charba, R. C. Wiggins, M. Goyal, B. L. Wharram, J. E. Wiggins, E. T. McCarthy, R. Sharma, M. Sharma, and V. J. Savin Antibodies to protein tyrosine phosphatase receptor type O (PTPro) increase glomerular albumin permeability (Palb) Am J Physiol Renal Physiol, July 1, 2009; 297(1): F138 - F144. [Abstract] [Full Text] [PDF]

				P. Luo, Y. Zhou, H.-H. Chang, J. Zhang, T. Seki, C.-Y. Wang, E. W. Inscho, and M.-H. Wang Glomerular 20-HETE, EETs, and TGF-{beta}1 in diabetic nephropathy Am J Physiol Renal Physiol, March 1, 2009; 296(3): F556 - F563. [Abstract] [Full Text] [PDF]

				J. Axelsson, A. Rippe, D. Venturoli, P. Sward, and B. Rippe Effects of early endotoxemia and dextran-induced anaphylaxis on the size selectivity of the glomerular filtration barrier in rats Am J Physiol Renal Physiol, February 1, 2009; 296(2): F242 - F248. [Abstract] [Full Text] [PDF]

				J. M. Williams, A. Sarkis, K. M. Hoagland, K. Fredrich, R. P. Ryan, C. Moreno, B. Lopez, J. Lazar, F. J. Fenoy, M. Sharma, et al. Transfer of the CYP4A region of chromosome 5 from Lewis to Dahl S rats attenuates renal injury Am J Physiol Renal Physiol, December 1, 2008; 295(6): F1764 - F1777. [Abstract] [Full Text] [PDF]

				S. Zhu, Y. Liu, L. Wang, and Q. H. Meng Transforming growth factor-{beta}1 is associated with kidney damage in patients with essential hypertension: renoprotective effect of ACE inhibitor and/or angiotensin II receptor blocker Nephrol. Dial. Transplant., September 1, 2008; 23(9): 2841 - 2846. [Abstract] [Full Text] [PDF]

				B. Haraldsson, J. Nystrom, and W. M. Deen Properties of the Glomerular Barrier and Mechanisms of Proteinuria Physiol Rev, April 1, 2008; 88(2): 451 - 487. [Abstract] [Full Text] [PDF]

				J. M. Williams, M. Sharma, S. Anjaiahh, J. R. Falck, and R. J. Roman Role of endogenous CYP450 metabolites of arachidonic acid in maintaining the glomerular protein permeability barrier Am J Physiol Renal Physiol, August 1, 2007; 293(2): F501 - F505. [Abstract] [Full Text] [PDF]

				J.-W. Gu, N. Tian, M. Shparago, W. Tan, A. P. Bailey, and R. D. Manning Jr. Renal NF-{kappa}B activation and TNF-{alpha} upregulation correlate with salt-sensitive hypertension in Dahl salt-sensitive rats Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2006; 291(6): R1817 - R1824. [Abstract] [Full Text] [PDF]

				K. Takeuchi, M. Renic, Q. C. Bohman, D. R. Harder, N. Miyata, and R. J. Roman Reversal of delayed vasospasm by an inhibitor of the synthesis of 20-HETE Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H2203 - H2211. [Abstract] [Full Text] [PDF]