Differential effects of TNF receptor 1 and 2 deletion on blood pressure and Ang II type I receptor (AT1R) expression

Abstract

Effects of either TNF receptor 1 (TNFR1), or receptor 2 (TNFR2), gene deletion were determined in a model of Ang II‐dependent hypertension. C57Bl/6J wildtype (WT), TNFR1−/−, and TNFR2−/− mice were given Ang II subcutaneously by osmotic minipump (1.6 ?g/min/kg) for 7 days. Systolic blood pressure (SBP) was measured by tailcuff and radiotelemetry. SBP was similar in untreated mice but higher in TNFR1−/− mice given Ang II (181±7 mmHg) compared to TNFR2−/− (147±3) and WT (163±6) mice. Radiotelemetry confirmed higher SBP in TNFR1−/− (149±2) compared to TNFR2−/− (143±2) and WT (143±1) mice. Food intake was similar but cumulative sodium excretion was elevated in TNFR1−/− versus TNFR2−/− and WT mice (132±9 vs 107±16 vs 118±9 ?mol/d/g body weight (BW), respectively). Urinary albumin was elevated in TNFR1−/− compared to TNFR2−/− and WT (1.35±0.17 vs 0.79±0.12 vs 0.93±0.14 ?g/mg creatinine, respectively). Water intake was higher in TNFR1−/− versus TNFR2−/− and WT mice (0.52±0.02 vs 0.45±0.01 vs 0.40±0.01 ml/d/g BW, respectively); urine volume also was higher in TNFR1−/− compared to TNFR2−/− and WT mice (0.24±0.02 vs 0.12±0.01 vs 0.15±0.01 ml/d/g BW, respectively). Renal cortical AT1R protein expression was elevated in TNFR1−/− mice compared to TNFR2−/− and WT mice. These data suggest that deletion of TNFR1 augments Ang II‐mediated increases in SBP, water intake, and sodium excretion associated with upregulation of AT1R.