Tumor necrosis factor alpha blockade increases renal Cyp2c23 expression and slows the progression of renal damage in salt-sensitive hypertension. Hypertension 2006 Mar;47(3):557-62
Date
01/18/2006Pubmed ID
16415373DOI
10.1161/01.HYP.0000198545.01860.90Scopus ID
2-s2.0-33644989494 (requires institutional sign-in at Scopus site) 100 CitationsAbstract
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.
Author List
Elmarakby AA, Quigley JE, Pollock DM, Imig JDMESH terms used to index this publication - Major topics in bold
AlbuminuriaAngiotensins
Animals
Blood Pressure
Cytochrome P-450 Enzyme System
Disease Progression
Etanercept
Hypertension
Immunoglobulin G
Kidney
Male
Proteinuria
Rats
Rats, Sprague-Dawley
Receptors, Tumor Necrosis Factor
Sodium Chloride, Dietary
Tumor Necrosis Factor-alpha