Regulation of nitric oxide consumption by hypoxic red blood cells.
The homeostasis of nitric oxide (NO) is attained through a balance between its production and consumption. Shifts in NO bioavailability have been linked to a variety of diseases. Although the regulation of NO production has been well documented, its consumption is largely thought to be unregulated. Here, we have demonstrated that under hypoxic conditions, NO accelerates its own consumption by increasing its entry into RBCs. When RBCs were exposed to NO (1:400 NO/heme ratio) under hypoxic conditions to form HbFe(II)NO, the consumption rate of NO increased significantly. This increase in NO consumption converted the bioactivity of serotonin from a vasodilator to a vasoconstrictor in isolated coronary arterioles. We identified HbFe(II)NO as a potential mediator of accelerated NO consumption. Accelerated NO consumption by HbFe(II)NO-bearing RBCs may contribute to hypoxic pulmonary vasoconstriction and the rebound effect seen on termination of NO inhalation therapy. Furthermore, accelerated NO consumption may exacerbate ischemia-mediated vasospasm and nitrate tolerance. Finally, this phenomenon may be an evolved mechanism to stabilize the vasculature in sepsis.
Han
Tae H
TH
Department of Chemical Engineering, University of California-Los Angeles, Los Angeles, CA 90095, USA.
Qamirani
Erion
E
Nelson
Allyson G
AG
Hyduke
Daniel R
DR
Chaudhuri
Gautam
G
Kuo
Lih
L
Liao
James C
JC
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D001160:Arterioles / Q000378:metabolism; D002417:Cattle; D015687:Cell Hypoxia / Q000502:physiology*; D003329:Coronary Vasospasm / Q000209:etiology / Q000503:physiopathology; D003331:Coronary Vessels / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology; D066298:In Vitro Techniques; D008954:Models, Biological; D009569:Nitric Oxide / Q000097:blood* / Q000378:metabolism / Q000627:therapeutic use; D011652:Pulmonary Circulation / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000503:physiopathology; D012701:Serotonin / Q000378:metabolism; D034421:Sus scrofa; D014662:Vasoconstrictor Agents / Q000378:metabolism; D014665:Vasodilator Agents / Q000378:metabolism
D006442:Glycated Hemoglobin; D006454:Hemoglobins; D009569:Nitric Oxide; D012701:Serotonin; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C058377:hemoglobin A, glycosylated-nitric oxide complex