TNF- inhibition reduces renal injury in DOCA-salt hypertensive rats
نویسندگان
چکیده
Elmarakby AA, Quigley JE, Imig JD, Pollock JS, Pollock DM. TNFinhibition reduces renal injury in DOCA-salt hypertensive rats. Am J Physiol Regul Integr Comp Physiol 294: R76–R83, 2008. First published November 7, 2007; doi:10.1152/ajpregu.00466.2007.—Studies suggest that the inflammatory cytokine TNFplays a role in the prognosis of end-stage renal diseases. We previously showed that TNFinhibition slowed the progression of hypertension and renal damage in angiotensin II salt-sensitive hypertension. Thus, we hypothesize that TNFcontributes 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 TNFinhibitor 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 TNFinhibition had no effect in the elevation of MAP in these rats (177 8 mmHg). Urinary protein excretion significantly increased in DOCAsalt 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); TNFinhibition 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 NFB activity also increased in DOCA-salt hypertensive rats, and etanercept treatment significantly reduced this effect. These data support the hypothesis that TNFcontributes to the increase in renal inflammation in DOCA-salt rats.
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