Tumor necrosis factor alpha blockade increases renal Cyp2c23 expression and slows the progression of renal damage in salt-sensitive hypertension.

Abstract

We hypothesized that the downregulation of Cyp2c by tumor necrosis factor (TNF) alpha 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-alpha 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-alpha contributes to downregulation of Cyp2c23, blood pressure regulation, and renal injury in angiotensin high-salt hypertension.

• Authors: Ahmed A Elmarakby, Jeffrey E Quigley, David M Pollock, John D Imig
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 47 Issue 3 Pg. 557-62 (Mar 2006) ISSN: 1524-4563 [Electronic] United States
• PMID: 16415373 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensins
• Cyp2c23 protein, rat
• Immunoglobulin G
• Receptors, Tumor Necrosis Factor
• Sodium Chloride, Dietary
• Tumor Necrosis Factor-alpha
• Cytochrome P-450 Enzyme System
• Cytochrome P-450 CYP2J2
• Etanercept

Topics

• Albuminuria (physiopathology)
• Angiotensins
• Animals
• Blood Pressure (drug effects)
• Cytochrome P-450 CYP2J2
• Cytochrome P-450 Enzyme System (metabolism)
• Disease Progression
• Etanercept
• Hypertension (chemically induced, metabolism, pathology, physiopathology)
• Immunoglobulin G (pharmacology)
• Kidney (metabolism, pathology)
• Male
• Proteinuria (physiopathology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Tumor Necrosis Factor
• Sodium Chloride, Dietary (pharmacology)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)