PMID- 18922887 OWN - NLM STAT- MEDLINE DCOM- 20090312 LR - 20181113 IS - 1931-857X (Print) IS - 1522-1466 (Electronic) IS - 1522-1466 (Linking) VI - 295 IP - 6 DP - 2008 Dec TI - Tumor necrosis factor-alpha induces renal vasoconstriction as well as natriuresis in mice. PG - F1836-44 LID - 10.1152/ajprenal.90297.2008 [doi] AB - Tumor necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of hypertension and renal injury. However, the direct effects of TNF-alpha on renal hemodynamic and excretory function are not yet clearly defined. We examined the renal responses to infusion of TNF-alpha (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-alpha infusion was initiated and 15 min were given for stabilization followed by another 60-min clearance period. TNF-alpha 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 micromol.min(-1).g(-1)) and fractional excretion of sodium (0.5 +/- 0.2 to 1.5 +/- 0.4%) without affecting arterial pressure. TNF-alpha also increased 8-isoprostane excretion (8.10 +/- 1.09 to 11.13 +/- 1.34 pg.min(-1).g(-1)). Pretreatment with TNF-alpha blocker etanercept (5 mg/kg sc; 24 and 3 h before TNF-alpha infusion; n = 6) abolished these responses. However, TNF-alpha induced an increase in RBF and caused attenuation of the GFR reduction in mice pretreated with superoxide (O(2)(-)) scavenger tempol (2 microg.g(-1).min(-1); n = 6). Pretreatment with nitric oxide (NO) synthase inhibitor nitro-l-arginine methyl ester (0.1 microg.g(-1).min(-1); n = 6) resulted in further enhancement in vasoconstriction while natriuresis remained unaffected in response to TNF-alpha. These data suggest that TNF-alpha induces renal vasoconstriction and hypofiltration via enhancing the activity of O(2)(-) and thus reducing the activity of NO. The natriuretic response to TNF-alpha is related to its direct effects on tubular sodium reabsorption. FAU - Shahid, Mohd AU - Shahid M AD - Dept. of Physiology, SL-39, Tulane Univ. Health Sciences Center, 1430 Tulane Ave., New Orleans, LA 70112, USA. FAU - Francis, Joseph AU - Francis J FAU - Majid, Dewan S A AU - Majid DS LA - eng GR - HL-66432/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20081015 PL - United States TA - Am J Physiol Renal Physiol JT - American journal of physiology. Renal physiology JID - 100901990 RN - 0 (Tumor Necrosis Factor-alpha) RN - 27415-26-5 (8-epi-prostaglandin F2alpha) RN - 9NEZ333N27 (Sodium) RN - B7IN85G1HY (Dinoprost) RN - RWP5GA015D (Potassium) SB - IM MH - Animals MH - Blood Flow Velocity/drug effects MH - Dinoprost/analogs & derivatives/urine MH - Glomerular Filtration Rate/drug effects MH - Hemodynamics/drug effects MH - Infusions, Intravenous MH - Kidney/drug effects/physiology MH - Mice MH - Mice, Inbred C57BL MH - Natriuresis/*drug effects MH - Potassium/urine MH - Renal Circulation/drug effects MH - Reverse Transcriptase Polymerase Chain Reaction MH - Sodium/urine MH - Tumor Necrosis Factor-alpha/administration & dosage/genetics/*pharmacology MH - Vasoconstriction/*drug effects PMC - PMC2604828 EDAT- 2008/10/17 09:00 MHDA- 2009/03/13 09:00 PMCR- 2008/10/15 CRDT- 2008/10/17 09:00 PHST- 2008/10/17 09:00 [pubmed] PHST- 2009/03/13 09:00 [medline] PHST- 2008/10/17 09:00 [entrez] PHST- 2008/10/15 00:00 [pmc-release] AID - 90297.2008 [pii] AID - F-90297-2008 [pii] AID - 10.1152/ajprenal.90297.2008 [doi] PST - ppublish SO - Am J Physiol Renal Physiol. 2008 Dec;295(6):F1836-44. doi: 10.1152/ajprenal.90297.2008. Epub 2008 Oct 15.