Tumor necrosis factor‐alpha (TNF‐α) induced natriuresis is prevented by blockade of distal tubular sodium transport in mice.

Abstract

We demonstrated earlier that acute TNF‐α administration in mice resulted in marked natriuresis despite its induction of renal vasoconstriction and hypofiltration. To examine whether this natriuresis is caused by a direct inhibitory action of TNF‐α on epithelial sodium transport, we assessed the renal responses to TNF‐α infusion (0.3 ng/min/g; i.v.) in anesthetized mice (n=6) pretreated with combined administration of amiloride (AM; 17 μg/kg/min; i.v.) and bendroflumethiazide (BZ; 2.8 μg/kg/min, i.v.) that would block distal tubular sodium transport. Renal blood flow (RBF) and glomerular filtration rate (GFR) were determined by PAH and inulin clearances. TNF‐α infusion in AM+BZ pretreated mice caused reductions of 35+8% in RBF (10.2±1.7 to 6.5±1.2 mL/min/g) and 43±6% in GFR (1.02±0.1 to 0.60±0.8 mL/min/g) with a slight decrease in mean arterial pressure (87±4 to 79+3 mmHg) which were similar to those observed in non‐treated mice reported earlier. However, contrary to the natriuretic response observed in non‐treated mice in our earlier study, TNF‐α in these AM+BZ pretreated mice resulted in a marked reduction of 64+9% in sodium excretion (4.4±0.3 to 1.5±0.3 μmol/min/g) with no significant change in fractional excretion of sodium (3.1±0.2 to 2.2±0.7%). These data suggest that TNF‐α induced natriuretic response results from its direct inhibitory action on distal tubular sodium transport.