Abstract
Inducible nitric oxide synthase (iNOS) catalyzes the formation of nitric oxide (NO) from L-arginine and O2. Although some O2 is required for this reaction, it is uncertain whether biologically relevant levels of hypoxia alter this pathway. We examined the effects of graded hypoxia on several steps in the iNOS pathway in lipopolysaccharide (LPS)-stimulated rat glomerular mesangial cells: induction of iNOS mRNA, NO synthesis, NO oxidation to nitrite (NO2-) and nitrate (NO3-), and accumulation of cGMP. Cultured cells were incubated for 24 hours in airtight flasks containing O2 (21%, 10%, 2.5%, and 0%), CO2 (5%), and N2 (balance), resulting in media PO2 levels of 140 +/- 3, 85 +/- 1, 46 +/- 3 (moderate hypoxia), and 32 +/- 5 (severe hypoxia) mm Hg, respectively. During normoxia (PO2, 85 to 140 mm Hg) LPS increased iNOS mRNA with associated increases in NO synthesis, NO2- and NO3- accumulation, and intracellular cGMP levels. In the absence of LPS, there was minimal NO synthesis and no detectable iNOS mRNA. Even during severe hypoxia, LPS elevated NO2- and NO3- relative to levels in unstimulated cells (P < .05), although to a lesser extent than during normoxia (P < .05). The induction of iNOS mRNA by LPS was preserved in hypoxia, and...Continue Reading
References
Nov 1, 1992·The Journal of Clinical Investigation·P J Shultz, L Raij
Nov 1, 1992·Chemical Research in Toxicology·W H KoppenolJ S Beckman
Apr 10, 1992·Science·Q W XieC Nathan
Apr 1, 1992·The Journal of Clinical Investigation·L De NicolaF B Gabbai
Jan 1, 1991·The Journal of Clinical Investigation·S AdnotP E Chabrier
May 30, 1991·The New England Journal of Medicine·A T Dinh-XuanJ Wallwork
Nov 15, 1989·Biochemical and Biophysical Research Communications·S L ArcherE K Weir
Dec 1, 1989·Clinical Science·J B WarrenP J Barnes
Aug 1, 1987·Journal of Applied Physiology·B M GrovesC S Houston
Oct 1, 1993·Journal of Applied Physiology·V HamplE K Weir
Jan 1, 1994·Journal of the American Society of Nephrology : JASN·A TojoK M Madsen
Feb 1, 1994·Journal of Applied Physiology·T C IsaacsonS L Archer
Jun 7, 1994·Proceedings of the National Academy of Sciences of the United States of America·D KunzJ Pfeilschifter
Aug 2, 1994·Proceedings of the National Academy of Sciences of the United States of America·S L ArcherE K Weir
Sep 1, 1994·Kidney International·M G MohauptB C Kone
Sep 1, 1994·Kidney International·P J ShultzM E Rosenberg
Jan 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·D A GellerT R Billiar
Feb 1, 1993·The Journal of Clinical Investigation·P J Shultz, J P Tolins
Feb 1, 1993·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·T M Lincoln, T L Cornwell
Feb 26, 1993·Biochemical and Biophysical Research Communications·Y NunokawaS Tanaka
Apr 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·D A GellerT R Billiar
Sep 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·L J IgnarroR E Byrns
Jul 1, 1993·The American Journal of Physiology·B E RobertsonM T Nelson
Feb 1, 1993·Journal of the American Society of Nephrology : JASN·L Raij, P J Shultz
Feb 1, 1993·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·S Archer
Jan 1, 1993·Journal of Applied Physiology·R D Russ, B R Walker
Citations
May 17, 1996·Neuroscience Letters·B MayerK Schmidt
Sep 17, 2013·Neuropharmacology·Wioletta MakuchBarbara Przewlocka
May 1, 1997·Disease-a-month : DM·R G KilbournC Szabó
Apr 27, 2000·Journal of Hepatology·C VargiuS Colombatto
Dec 31, 1996·Brain Research. Molecular Brain Research·N R PrabhakarR N Kalaria
Jun 27, 2003·Nitric Oxide : Biology and Chemistry·Susana Castro-BlancoJosé Rodrigo
Sep 6, 2000·The Biochemical Journal·C C McCormickM Calero
Jul 22, 1998·Critical Care Medicine·M J MorinM P Fink
Jun 3, 2000·Annual Review of Pharmacology and Toxicology·Y Z GuC A Bradfield
Dec 26, 2001·American Journal of Respiratory Cell and Molecular Biology·Bruce R Pitt, Claudette M St Croix
Apr 25, 2003·Journal of Pharmaceutical Sciences·Micheal S Guirguis, Fakhreddin Jamali
Oct 1, 2011·Free Radical Biology & Medicine·Mary A RobinsonCynthia M Otto
Jul 18, 2015·International Immunopharmacology·K P MishraShashi Bala Singh
Mar 6, 2012·International Journal of Cardiology·Dimitrios KarakitsosPeriklis Davlouros
Feb 7, 2004·Cell Transplantation·M de GrootR van Schilfgaarde
Feb 23, 1999·Clinical and Experimental Pharmacology & Physiology·D V Faller
Jan 19, 2000·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Q ShiK Xie
May 20, 2005·American Journal of Physiology. Cell Physiology·S C Land, C Rae
Feb 15, 2008·American Journal of Physiology. Cell Physiology·Mary A RobinsonCynthia M Otto
Feb 24, 2001·American Journal of Physiology. Cell Physiology·C M Otto, J E Baumgardner
May 13, 2003·Scandinavian Journal of Gastroenterology·C von BothmerL Fändriks
Jan 14, 1999·The American Journal of Physiology·A KumarJ E Parrillo
Jan 25, 2000·American Journal of Physiology. Endocrinology and Metabolism·M B Ganz, A Seftel
Apr 13, 1999·The American Journal of Physiology·K SatoI F McMurtry
Nov 1, 2003·Cell Transplantation·M de GrootR Van Schilfgaarde
Sep 12, 2003·Experimental Biology and Medicine·Alfredo GrilliMario Felaco
Mar 15, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Karen S Mark, Thomas P Davis
Feb 19, 2000·Biochemical and Biophysical Research Communications·Y HongN Yamada
Feb 9, 2000·Journal of the American Society of Nephrology : JASN·Masao KakokiMasao Omata