Red blood cells prevent inhibition of hypoxic pulmonary vasoconstriction by nitrite in isolated, perfused rat lungs.
Nitrite reduction to nitric oxide (NO) may be potentiated by a nitrite reductase activity of deoxyHb and contribute to systemic hypoxic vasodilation. The effect of nitrite on the pulmonary circulation has not been well characterized. We explored the effect of nitrite on hypoxic pulmonary vasoconstriction (HPV) and the role of the red blood cell (RBC) in nitrite reduction and nitrite-mediated vasodilation. As to method, isolated rat lungs were perfused with buffer, or buffer with RBCs, and subjected to repeated hypoxic challenges, with or without nitrite. As a result, in buffer-perfused lungs, HPV was reduced at nitrite concentrations of 7 muM and above. Nitrite inhibition of HPV was prevented by excess free Hb and RBCs, suggesting that vasodilation was mediated by free NO. Nitrite-inhibition of HPV was not potentiated by mild acidosis (pH = 7.2) or xanthine oxidase activity. RBCs at 15% but not 1% hematocrit prevented inhibition of HPV by nitrite (maximum nitrite concentration of approximately 35 muM) independent of perfusate Po(2). Degradation of nitrite was accelerated by hypoxia in the presence of RBCs but not during buffer perfusion. In conclusion, low micromolar concentrations of nitrite inhibit HPV in buffer-perfused lungs and when RBC concentration is subphysiological. This effect is lost when RBC concentration approaches physiological levels, despite enhanced nitrite degradation in the presence of RBCs. These data suggest that, although deoxyHb may generate NO from nitrite, insufficient NO escapes the RBC to cause vasodilation in the pulmonary circulation under the dynamic conditions of blood flow through the lungs and that RBCs are net scavengers of NO.
Deem
Steven
S
Department of Anesthesiology, University of Washington, Seattle, WA, USA. sdeem@u.washington.edu
Min
Jin-Hye
JH
Moulding
Jennifer D
JD
Eveland
Randy
R
Swenson
Erik R
ER
D000138:Acidosis / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001944:Breath Tests; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D010477:Perfusion; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012977:Sodium Nitrite / Q000378:metabolism* / Q000494:pharmacology; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014969:Xanthine Oxidase / Q000378:metabolism
D006454:Hemoglobins; D009569:Nitric Oxide; D014969:Xanthine Oxidase; D012977:Sodium Nitrite