TNF-α inhibition reduces renal injury in DOCA-salt hypertensive rats

Ahmed A. Elmarakby, Jeffrey E. Quigley, John D. Imig, Jennifer S. Pollock, David M. Pollock

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

Studies suggest that the inflammatory cytokine TNF-α plays a role in the prognosis of end-stage renal diseases. We previously showed that TNF-α inhibition slowed the progression of hypertension and renal damage in angiotensin II salt-sensitive hypertension. Thus, we hypothesize that TNF-α contributes to renal inflammation in a model of mineralocorticoid- induced hypertension. Four groups of rats (n = 5 or 6) were studied for 3 wk with the following treatments: 1) placebo, 2) placebo + TNF-α inhibitor etanercept (1.25 mg·kg-1·day-1 sc), 3) deoxycorticosterone acetate + 0.9% NaCl to drink (DOCA-salt), or 4) DOCA-salt + etanercept. Mean arterial blood pressure (MAP) measured by telemetry increased in DOCA-salt rats compared with baseline (177 ± 4 vs. 107 ± 3 mmHg; P < 0.05), and TNF-α inhibition had no effect in the elevation of MAP in these rats (177 ± 8 mmHg). Urinary protein excretion significantly increased in DOCA-salt rats compared with placebo (703 ± 76 vs. 198 ± 5 mg/day); etanercept lowered the proteinuria (514 ± 64 mg/day; P < 0.05 vs. DOCA-salt alone). Urinary albumin excretion followed a similar pattern in each group. Urinary monocyte chemoattractant protein (MCP)-1 and endothelin (ET)-1 excretion were also increased in DOCA-salt rats compared with placebo (MCP-1: 939 ± 104 vs. 43 ± 7 ng/day, ET-1: 3.30 ± 0.29 vs. 1.07 ± 0.03 fmol/day; both P < 0.05); TNF-α inhibition significantly decreased both MCP-1 and ET-1 excretion (409 ± 138 ng/day and 2.42 ± 0.22 fmol/day, respectively; both P < 0.05 vs. DOCA-salt alone). Renal cortical NF-κB activity also increased in DOCA-salt hypertensive rats, and etanercept treatment significantly reduced this effect. These data support the hypothesis that TNF-α contributes to the increase in renal inflammation in DOCA-salt rats.

Original languageEnglish (US)
Pages (from-to)R76-R83
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume294
Issue number1
DOIs
StatePublished - Jan 1 2008

Keywords

  • Blood pressure
  • Deoxycorticosterone acetate
  • Etanercept
  • Nuclear factor-κB
  • Renal inflammation
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'TNF-α inhibition reduces renal injury in DOCA-salt hypertensive rats'. Together they form a unique fingerprint.

  • Cite this