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This Article Full Text Full Text (PDF) All Versions of this Article: 295/6/F1836    most recent 90297.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Shahid, M. Articles by Majid, D. S. A. Search for Related Content PubMed PubMed Citation Articles by Shahid, M. Articles by Majid, D. S. A.

Tumor necrosis factor- induces renal vasoconstriction as well as natriuresis in mice

¹Department of Physiology, Tulane University Health Sciences Center, New Orleans; and ²Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana

Submitted 7 May 2008 ; accepted in final form 8 October 2008

Tumor necrosis factor- (TNF-) has been implicated in the pathogenesis of hypertension and renal injury. However, the direct effects of TNF- on renal hemodynamic and excretory function are not yet clearly defined. We examined the renal responses to infusion of TNF- (0.33 ng·g^–1·min^–1) in anesthetized mice. Renal blood flow (RBF) and glomerular filtration rate (GFR) were determined by PAH and inulin clearance. The urine was collected from a cannula inserted into the bladder. Following the 60-min control clearance period, TNF- infusion was initiated and 15 min were given for stabilization followed by another 60-min clearance period. TNF- alone (n = 7) caused decreases in RBF (7.9 ± 0.3 to 6.4 ± 0.3 ml·min^–1·g^–1) and GFR (1.04 ± 0.06 to 0.62 ± 0.08 ml·min^–1·g^–1) as well as increases in absolute (0.8 ± 0.3 to 1.4 ± 0.3 µmol·min^–1·g^–1) and fractional excretion of sodium (0.5 ± 0.2 to 1.5 ± 0.4%) without affecting arterial pressure. TNF- also increased 8-isoprostane excretion (8.10 ± 1.09 to 11.13 ± 1.34 pg·min^–1·g^–1). Pretreatment with TNF- blocker etanercept (5 mg/kg sc; 24 and 3 h before TNF- infusion; n = 6) abolished these responses. However, TNF- induced an increase in RBF and caused attenuation of the GFR reduction in mice pretreated with superoxide (O₂^–) scavenger tempol (2 µg·g^–1·min^–1; n = 6). Pretreatment with nitric oxide (NO) synthase inhibitor nitro-L-arginine methyl ester (0.1 µg·g^–1·min^–1; n = 6) resulted in further enhancement in vasoconstriction while natriuresis remained unaffected in response to TNF-. These data suggest that TNF- induces renal vasoconstriction and hypofiltration via enhancing the activity of O₂^– and thus reducing the activity of NO. The natriuretic response to TNF- is related to its direct effects on tubular sodium reabsorption.

superoxide; nitric oxide; renal hemodynamic; sodium excretion