Pulmonary vascular effects of red blood cells containing S-nitrosated hemoglobin.
The role of S-nitrosated hemoglobin (SNO-Hb) in the regulation of blood flow is a central and controversial question in cardiopulmonary physiology. In the present study, we investigate whether intact human red blood cells (RBCs) synthesized to contain high SNO-Hb levels are able to export nitric oxide bioactivity and vasodilate the pulmonary circulation, and whether SNO-Hb dependent vasodilation occurs secondary to an intrinsic oxygen-linked, allosteric function of Hb. RBCs containing supraphysiological concentrations (100-1,000x normal) of SNO-Hb (SNO-RBCs) were synthesized and added to isolated, perfused rat lungs during anoxic or normoxic ventilation, and during normoxic ventilation with pulmonary hypertension induced by the thromboxane mimetic U-46619. SNO-RBCs produced dose-dependent pulmonary vasodilation compared with control RBCs during conditions of both normoxic (U-46619) and hypoxic pulmonary vasoconstriction. These effects were associated with a simultaneous, rapid, and temperature-dependent loss of SNO from Hb. Both vasodilatory effects and the rate of SNO-Hb degradation were independent of oxygen tension and Hb oxygen saturation. Furthermore, these effects were not affected by inhibition of the RBC membrane band 3 protein (anion exchanger-1), a putative membrane facilitator of NO export from RBCs. Whereas these data support observations by multiple groups that synthesized SNO-Hb can vasodilate, this effect is not under intrinsic oxygen-dependent allosteric control, nor likely to be relevant in the pulmonary circulation at normal physiological concentrations.
Deem
Steven
S
Dept. of Anesthesiology, PO Box 359724, Harborview Medical Center, Seattle, WA 98104-2499, USA. sdeem@u.washington.edu
Kim
Seong Su
SS
Min
Jin-Hye
JH
Eveland
Randy
R
Moulding
Jennifer
J
Martyr
Sabrina
S
Wang
Xunde
X
Swenson
Erik R
ER
Gladwin
Mark T
MT
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism; D004912:Erythrocytes / Q000502:physiology*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D015538:Nitrosation; D010100:Oxygen / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D001457:Anion Exchange Protein 1, Erythrocyte; D006454:Hemoglobins; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D010100:Oxygen