title: Involvement of tumor necrosis factor-alpha in natriuretic response to systemic infusion of nitric oxide synthase inhibitor in anesthetized mice.
abstract: Systemic infusion of TNF-alpha 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 acute NO blockade systemically induces TNF-alpha generation. which induces this natriuretic response. Renal responses to intravenous infusion of the NO synthase inhibitor nitro-L-arginine methyl ester (L-NAME; 0.2 microg x min(-1) x g body wt(-1) for 85 min) and its impact on the plasma level of TNF-alpha were evaluated in anesthetized mice. Plasma TNF-alpha 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-alpha protein expression in kidney tissue. L-NAME infusion caused a 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 x min(-1) x g(-1); P < 0.01) and glomerular filtration rate (GFR; 1.14 +/- 0.07 to 0.77 +/- 0.04 ml x min(-1) x g(-1); P < 0.01) with a marked increase in sodium excretion (U(Na)V; 0.48 +/- 0.10 to 3.52 +/- 0.85 micromol x min(-1) x g(-1); P < 0.01). Interestingly, in mice (n = 7) pretreated with the TNF-alpha blocker etanercept (5 mg/kg sc), the U(Na)V response to l-NAME infusion was markedly blunted (0.58 +/- 0.08 to 1.22 +/- 0.28 micromol x min(-1) x g(-1); P = NS) although responses for MAP, RBF, and GFR were mostly unchanged. However, pretreatment with the superoxide scavenger tempol in mice (n = 7) did not alter the U(Na)V response to L-NAME. These data demonstrate that L-NAME-induced natriuresis is mediated, at least in part, by concomitant generation of TNF-alpha during NO blockade.
authors.affiliation: Department of Physiology and Tulane Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Mohd
authors.initials: M
authors.lastname: Shahid
authors.forename: Joseph
authors.initials: J
authors.lastname: Francis
authors.forename: Khalid
authors.initials: K
authors.lastname: Matrougui
authors.forename: Dewan S A
authors.initials: DS
authors.lastname: Majid
mesh_terms: D000768:Anesthesia, General; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000008:administration & dosage; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D000068800:Etanercept; D016166:Free Radical Scavengers / Q000008:administration & dosage; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007074:Immunoglobulin G / Q000008:administration & dosage; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage*; D009318:Natriuresis / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage; D012079:Renal Circulation / Q000187:drug effects; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000097:blood*; D015854:Up-Regulation
chemical_list: D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D013113:Spin Labels; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000068800:Etanercept; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester
references.citation: Circulation. 2002 May 7;105(18):2198-205
references.pmid: 11994255
references.citation: Am J Physiol. 1992 Jan;262(1 Pt 2):F40-6
references.pmid: 1733296
references.citation: Am J Physiol Regul Integr Comp Physiol. 2006 Dec;291(6):R1817-24
references.pmid: 16840655
references.citation: Crit Care Med. 2006 Feb;34(2):484-91
references.pmid: 16424732
references.citation: Hypertension. 1992 Apr;19(4):333-8
references.pmid: 1313394
references.citation: Am J Physiol Regul Integr Comp Physiol. 2008 Jan;294(1):R76-83
references.pmid: 17989143
references.citation: Am J Physiol Regul Integr Comp Physiol. 2004 Jul;287(1):R27-32
references.pmid: 15044181
references.citation: Acta Anaesthesiol Scand. 1999 Mar;43(3):275-88
references.pmid: 10081533
references.citation: Am J Physiol Renal Physiol. 2008 Sep;295(3):F758-64
references.pmid: 18596078
references.citation: Am J Hypertens. 2008 Apr;21(4):477-81
references.pmid: 18246055
references.citation: Am J Physiol Renal Physiol. 2008 Dec;295(6):F1836-44
references.pmid: 18922887
references.citation: Hypertension. 2007 Jan;49(1):193-200
references.pmid: 17075027
references.citation: Mol Cell Biochem. 2008 May;312(1-2):103-12
references.pmid: 18320293
references.citation: Brain Res. 2008 Aug 21;1226:89-98
references.pmid: 18620339
references.citation: Am J Physiol Heart Circ Physiol. 2007 Nov;293(5):H2726-37
references.pmid: 17675574
references.citation: Shock. 2001 Sep;16(3):211-7
references.pmid: 11531023
references.citation: Circulation. 2004 Oct 5;110(14):2003-9
references.pmid: 15451797
references.citation: Oral Microbiol Immunol. 2006 Dec;21(6):360-5
references.pmid: 17064393
references.citation: J Am Soc Nephrol. 1990 Dec;1(6):875-81
references.pmid: 2103847
references.citation: Circ Res. 1993 Mar;72(3):511-6
references.pmid: 8431981
references.citation: Hypertension. 1993 Oct;22(4):535-41
references.pmid: 8406658
references.citation: Am J Physiol. 1995 Jun;268(6 Pt 2):F1004-8
references.pmid: 7611442
references.citation: Am J Hypertens. 2001 Jun;14(6 Pt 2):74S-82S
references.pmid: 11411769
references.citation: Am J Physiol. 1995 Jul;269(1 Pt 2):F17-21
references.pmid: 7631827
references.citation: Am J Respir Cell Mol Biol. 1997 Sep;17(3):279-83
references.pmid: 9308913
references.citation: Hypertens Res. 2005 May;28(5):475-82
references.pmid: 16156512
references.citation: Am J Physiol Regul Integr Comp Physiol. 2007 Apr;292(4):R1479-85
references.pmid: 17218445
references.citation: J Nutr Biochem. 2008 Dec;19(12):833-9
references.pmid: 18479899
references.citation: Shock. 2000 Mar;13(3):217-23
references.pmid: 10718379
references.citation: Hypertension. 1995 Mar;25(3):408-14
references.pmid: 7875767
references.citation: Am J Physiol Heart Circ Physiol. 2008 Jul;295(1):H69-76
references.pmid: 18456735
references.citation: J Immunol. 1993 Aug 1;151(3):1548-61
references.pmid: 8393046
references.citation: Clin Exp Immunol. 2002 Jul;129(1):4-10
references.pmid: 12100016
references.citation: Vascul Pharmacol. 2008 Feb-Mar;48(2-3):115-21
references.pmid: 18295546
references.citation: Clin Exp Pharmacol Physiol. 2007 Nov;34(11):1173-80
references.pmid: 17880373
references.citation: Cytokine. 2006 Feb 7;33(3):138-44
references.pmid: 16488623
references.citation: Am J Physiol. 1993 Jan;264(1 Pt 2):F79-87
references.pmid: 8430833
references.citation: J Am Soc Nephrol. 1999 Dec;10(12):2631-6
references.pmid: 10589704
references.citation: J Am Soc Nephrol. 1992 Mar;2(9):1371-87
references.pmid: 1627761
references.citation: Am J Physiol. 1993 Mar;264(3 Pt 2):F458-66
references.pmid: 8456958
references.citation: Hypertension. 2006 Mar;47(3):568-72
references.pmid: 16401762
references.citation: Am J Physiol Renal Physiol. 2007 Oct;293(4):F1178-86
references.pmid: 17634398
references.citation: J Exp Med. 2007 Oct 1;204(10):2449-60
references.pmid: 17875676
references.citation: Am J Physiol Heart Circ Physiol. 2007 Dec;293(6):H3388-95
references.pmid: 17921322
references.citation: Microbes Infect. 2009 Jan;11(1):123-32
references.pmid: 19063988
references.citation: Shock. 2010 Sep;34(3):281-90
references.pmid: 19997049
references.citation: Clin Exp Pharmacol Physiol. 1997 Aug;24(8):591-4
references.pmid: 9269533
references.citation: Am J Physiol Heart Circ Physiol. 2004 Jun;286(6):H2264-71
references.pmid: 15148057