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

Ahmed Abdelrazik Elmarakby, Jeffrey E. Quigley, David M. Pollock, John D. Imig

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

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

Original languageEnglish (US)
Pages (from-to)557-562
Number of pages6
JournalHypertension
Volume47
Issue number3 II
DOIs
StatePublished - Mar 1 2006

Fingerprint

Angiotensins
Tumor Necrosis Factor-alpha
Salts
Hypertension
Kidney
Epoxide Hydrolases
Arterial Pressure
Down-Regulation
Blood Pressure
Renal Hypertension
Albuminuria
Chemokine CCL2
Wounds and Injuries
Etanercept
Proteinuria
Angiotensin II
Sprague Dawley Rats
Monocytes
Macrophages
Diet

Keywords

  • Angiotensin
  • Blood pressure
  • Metabolism
  • Proteinuria
  • Sodium, dietary
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Tumor necrosis factor α blockade increases renal Cyp2c23 expression and slows the progression of renal damage in salt-sensitive hypertension. / Elmarakby, Ahmed Abdelrazik; Quigley, Jeffrey E.; Pollock, David M.; Imig, John D.

In: Hypertension, Vol. 47, No. 3 II, 01.03.2006, p. 557-562.

Research output: Contribution to journalArticle

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

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KW - Metabolism

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KW - Sodium, dietary

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