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

• DOI: 10.1152/ajpregu.00466.2007
• Publication Date: 2007-11-07T20:47:46Z
• Authors: Ahmed A. Elmarakby; Jeffrey E. Quigley; John D. Imig; Jennifer S. Pollock; David M. Pollock
• Keywords: Inflammation; Male; 0301 basic medicine; Endothelin-1; Tumor Necrosis Factor-alpha; Anti-Inflammatory Agents, Non-Steroidal; NF-kappa B; Blood Pressure; Kidney; Receptors, Tumor Necrosis Factor; Etanercept; Rats; Rats, Sprague-Dawley; Disease Models, Animal; 03 medical and health sciences; Immunoglobulin G; Mineralocorticoids; Hypertension; Animals; Kidney Diseases; Desoxycorticosterone; Chemokine CCL2

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