PMID- 8226460 OWN - NLM STAT- MEDLINE DCOM- 19931203 LR - 20171213 IS - 8750-7587 (Print) IS - 0161-7567 (Linking) VI - 75 IP - 2 DP - 1993 Aug TI - NG-monomethyl-L-arginine does not restore loss of hypoxic pulmonary vasoconstriction induced by TNF-alpha. PG - 618-25 AB - Tumor necrosis factor-alpha (TNF-alpha) causes systemic hypotension, pulmonary vasodilation, and loss of hypoxic pulmonary vasoconstriction. NG-monomethyl-L-arginine (L-NMMA) inhibits nitric oxide (NO) production and prevents some systemic manifestations of TNF-alpha. We tested using an isolated perfused canine lobe whether NO also mediates the pulmonary vascular effects of TNF-alpha. Total resistance (RT) was measured during control and hypoxic ventilation over a 90-min period in six control lobes, five lobes treated with TNF-alpha (250 micrograms), six lobes treated with L-NMMA (200 mg), and five lobes treated with L-NMMA (200 mg) + TNF-alpha (250 micrograms). In the control lobes RT increased (P < 0.02) from 0.0474 +/- 0.0105 to 0.0677 +/- 0.0133 cmH2O.ml-1 x min during normoxic and hypoxic ventilation, respectively. RT decreased (P < 0.05) from a baseline of 0.0593 +/- 0.0133 to 0.0449 +/- 0.0176 cmH2O.ml-1 x min 30 min after TNF-alpha administration and did not further change during hypoxic ventilation (0.0475 +/- 0.0107 cmH2O.ml-1 x min). L-NMMA pretreatment did not prevent the TNF-alpha-induced loss of hypoxic pulmonary vasoconstriction, with values of RT unchanged from normoxic (0.0541 +/- 0.0067 cmH2O.ml-1 x min) to hypoxic (0.0545 +/- 0.0078 cmH2O.ml-1.min) ventilation (P > 0.10) in the L-NMMA + TNF-alpha group after TNF-alpha administration. We conclude that NO is not the mediator responsible for the acute pulmonary vascular effects of TNF-alpha. FAU - Johnson, D AU - Johnson D AD - Department of Medicine, University of Saskatchewan, Saskatoon, Canada. FAU - Hurst, T AU - Hurst T FAU - Wilson, T AU - Wilson T FAU - Murphy, F AU - Murphy F FAU - Saxema, A AU - Saxema A FAU - To, T AU - To T FAU - Mayers, I AU - Mayers I LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Appl Physiol (1985) JT - Journal of applied physiology (Bethesda, Md. : 1985) JID - 8502536 RN - 0 (Tumor Necrosis Factor-alpha) RN - 27JT06E6GR (omega-N-Methylarginine) RN - 31C4KY9ESH (Nitric Oxide) RN - 94ZLA3W45F (Arginine) RN - DCR9Z582X0 (Epoprostenol) SB - IM MH - Animals MH - Arginine/*analogs & derivatives/pharmacology MH - Blood Cell Count MH - Blood Gas Analysis MH - Blood Pressure/physiology MH - Dogs MH - Epoprostenol/pharmacology MH - Filtration MH - Granulocytes/physiology MH - Hypoxia/*physiopathology MH - Nitric Oxide/*antagonists & inhibitors/physiology MH - Perfusion MH - Pulmonary Circulation/*drug effects MH - Pulmonary Wedge Pressure/drug effects MH - Respiration, Artificial MH - Tumor Necrosis Factor-alpha/*pharmacology MH - Vascular Resistance/physiology MH - Vasoconstriction/*drug effects MH - omega-N-Methylarginine EDAT- 1993/08/01 00:00 MHDA- 1993/08/01 00:01 CRDT- 1993/08/01 00:00 PHST- 1993/08/01 00:00 [pubmed] PHST- 1993/08/01 00:01 [medline] PHST- 1993/08/01 00:00 [entrez] AID - 10.1152/jappl.1993.75.2.618 [doi] PST - ppublish SO - J Appl Physiol (1985). 1993 Aug;75(2):618-25. doi: 10.1152/jappl.1993.75.2.618.