title: Influence of oxygen, temperature and carbon dioxide on nitric oxide formation from nitrite as measured in expired gas from in situ perfused rabbit lungs.
abstract: In biological systems, nitric oxide (NO) may be generated non-enzymatically from nitrite (nitrite-derived NO), in addition to nitric oxide synthase-catalyzed (NOS-derived) L-arginine-dependent formation. Through recordings of expired NO, we studied the influence of temperature on NOS- and nitrite-derived NO in the perfused lung. We also studied the impact of other influencing factors (O(2), CO(2), and pH) on nitrite-derived NO in the same system. Both NO-generating systems exhibited biphasic temperature dependence with a positive correlation between temperature and NO generation that peaked between 42 and 44 degrees C. The nitrite-derived NO generation was enhanced by hypoxia alone (>20 x after 5 min) and further by concomitant increase in CO(2). The CO(2) effect could not be explained by changes in extracellular pH and was unaltered by acetazolamide. We conclude that the temperature dependence in the known enzyme-catalyzed NOS-derived NO and especially in the nitrite-derived NO strengthens the hypothesis that an enzyme could be involved in nitrite-derived NO formation. The enhancement of nitrite-derived NO by increases in CO(2) suggests that this system could be of importance to improve perfusion in ischemic tissues.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institute, S-171 77 Stockholm, Sweden. per.agvald@fyfa.ki.se
authors.forename: Per
authors.initials: P
authors.lastname: Agvald
authors.forename: L Christofer
authors.initials: LC
authors.lastname: Adding
authors.forename: Lars E
authors.initials: LE
authors.lastname: Gustafsson
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism; D002245:Carbon Dioxide / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology*; D010477:Perfusion; D011817:Rabbits; D013696:Temperature
chemical_list: D004791:Enzyme Inhibitors; D009573:Nitrites; D002245:Carbon Dioxide; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester