Systemic infusion of tumor necrosis factor-alpha (TNF-α) exerts renal vasoconstriction but caused marked natriuresis in mice. Similar renal responses were also observed during systemic infusion of nitric oxide (NO) synthase inhibitors as opposed to their usual antinatriuretic responses when administered intrarenally. In the present study, we examined the hypothesis that the acute NO blockade systemically induces TNF-α generation which induces this natriuretic response Renal responses to intravenous infusion of NO synthase inhibitor, nitro-L-arginine methyl ester (L-NAME; 0.2 μg/min/g bw for 85 min) and its' impact on plasma level of TNF-α were evaluated in anesthetized mice. The plasma TNF-α was undetected in untreated mice (n=7) but was elevated in L-NAME treated mice (109±22 pg/mL; p<0.01 vs untreated group; n=7) along with an increase in TNF-α protein expression in kidney tissue. L-NAME infusion caused usual increase in mean arterial pressure (MAP; 98±3 to 122±3 mmHg; p<0.01) and decreases in renal blood flow (RBF; 8.6±0.3 to 4.4±0.2 mL/min/g; p<0.01) and glomerular filtration rate (GFR; 1.14±0.07 to 0.77±0.04 mL/min/g; p<0.01) with a marked increase in sodium excretion (UNaV; 0.48±0.10 to 3.52±0.85 μmol/min/g; p<0.01). Interestingly, in mice (n=7) pretreated with TNF-α blocker etanercept (5 mg/kg, s.c), the UNaV response to L-NAME infusion was markedly blunted (0.58±0.08 to 1.22±0.28 μmol/min/g; p=NS) though responses on MAP, RBF and GFR were mostly unchanged. However, pretreatment with superoxide scavenger, tempol in mice (n=7) did not alter the UNaV response to L-NAME. These data demonstrate that L-NAME-induced natriuresis is mediated, at least in part, by concomitant generation of TNF-α during NO blockade.
- Nitric Oxide
- Renal hemodynamics
- Copyright © 2009, American Journal of Physiology - Renal Physiology