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(Hypertension. 2006;47:557.)
© 2006 American Heart Association, Inc.

Part 2 Original Articles

Tumor Necrosis Factor Blockade Increases Renal Cyp2c23 Expression and Slows the Progression of Renal Damage in Salt-Sensitive Hypertension

From the Departments of Physiology (A.A.E., J.E.Q., D.M.P.) and Surgery (D.M.P., J.D.I.) and Vascular Biology Center (D.M.P., J.D.I.), Medical College of Georgia, Augusta.

Correspondence to John D. Imig, Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912-2500. E-mail jdimig{at}mail.mcg.edu

We hypothesized that the downregulation of Cyp2c by tumor necrosis factor (TNF) contributes to hypertension and renal injury in salt-sensitive angiotensin hypertension. Male Sprague-Dawley rats were fed a high-salt diet (8% NaCl), and osmotic minipumps were implanted to deliver angiotensin II for 14 days. Rats were divided into 3 groups: high salt, angiotensin high salt, and angiotensin high salt administered the TNF- blocker, etanercept. Arterial pressure increased from 94±5 to 148±7 mm Hg during week 1 in the angiotensin high-salt group, whereas etanercept slowed blood pressure elevation during the first week in the treated group (90±2 to 109±6 mm Hg). After 2 weeks, arterial pressure increased to 156±11 mm Hg in the angiotensin high-salt group and 141±6 mm Hg in the etanercept-treated group. Albuminuria and proteinuria were significantly elevated in angiotensin high-salt rats and were reduced in the etanercept-treated rats. Urinary monocyte chemoattractant protein-1 excretion significantly increased in the angiotensin high-salt group (275±47 versus 81±19 ng/day) and was decreased in the etanercept-treated group (153±31 ng/day). Angiotensin high-salt rats also had a significant increase in renal monocyte/macrophage infiltration, and this was again attenuated by etanercept treatment. Renal expression of Cyp2c23 decreased, whereas renal epoxide hydrolase expression increased in angiotensin high-salt rats. Etanercept treatment increased Cyp2c23 expression and lowered epoxide hydrolase expression. These data suggest that TNF- contributes to downregulation of Cyp2c23, blood pressure regulation, and renal injury in angiotensin high-salt hypertension.

Key Words: sodium, dietary • angiotensin • tumor necrosis factor • blood pressure • proteinuria • metabolism

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