This Article Full Text Full Text (PDF) All Versions of this Article: 47/3/557    most recent 01.HYP.0000198545.01860.90v1 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 Elmarakby, A. A. Articles by Imig, J. D. Search for Related Content PubMed PubMed Citation Articles by Elmarakby, A. A. Articles by Imig, J. D. Related Collections Animal models of human disease Other hypertension Hypertension - basic studies Peripheral vascular disease Lipid and lipoprotein metabolism

(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

This article has been cited by other articles:

				M. Shahid, J. Francis, and D. S. A. Majid Tumor necrosis factor-{alpha} induces renal vasoconstriction as well as natriuresis in mice Am J Physiol Renal Physiol, December 1, 2008; 295(6): F1836 - F1844. [Abstract] [Full Text] [PDF]

				S. Sriramula, M. Haque, D. S.A. Majid, and J. Francis Involvement of Tumor Necrosis Factor-{alpha} in Angiotensin II-Mediated Effects on Salt Appetite, Hypertension, and Cardiac Hypertrophy Hypertension, May 1, 2008; 51(5): 1345 - 1351. [Abstract] [Full Text] [PDF]

				A. A. Elmarakby, J. E. Quigley, J. D. Imig, J. S. Pollock, and D. M. Pollock TNF-{alpha} inhibition reduces renal injury in DOCA-salt hypertensive rats Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2008; 294(1): R76 - R83. [Abstract] [Full Text] [PDF]

				A. A. Elmarakby, J. E. Quigley, J. J. Olearczyk, A. Sridhar, A. K. Cook, E. W. Inscho, D. M. Pollock, and J. D. Imig Chemokine Receptor 2b Inhibition Provides Renal Protection in Angiotensin II Salt Hypertension Hypertension, December 1, 2007; 50(6): 1069 - 1076. [Abstract] [Full Text] [PDF]

				T. J. Guzik, N. E. Hoch, K. A. Brown, L. A. McCann, A. Rahman, S. Dikalov, J. Goronzy, C. Weyand, and D. G. Harrison Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction J. Exp. Med., October 1, 2007; 204(10): 2449 - 2460. [Abstract] [Full Text] [PDF]

				M. J. Socha, M. Manhiani, N. Said, J. D. Imig, and K. Motamed Secreted Protein Acidic and Rich in Cysteine Deficiency Ameliorates Renal Inflammation and Fibrosis in Angiotensin Hypertension Am. J. Pathol., October 1, 2007; 171(4): 1104 - 1112. [Abstract] [Full Text] [PDF]