Published online before print February 21, 2005, doi: 10.1161/01.HYP.0000153791.89776.43
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(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
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 (Palb) 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 Palb 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 Palb 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 Palb 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 Palb and opposed the effects of TGF-ß to increase Palb. 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 Palb through inhibition of the glomerular production of 20-HETE.
Key Words: transforming growth factors • kidney • hypertension, renal
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