title: Inhaled nitric oxide augments nitric oxide transport on sickle cell hemoglobin without affecting oxygen affinity.
abstract: Nitric oxide (NO) inhalation has been reported to increase the oxygen affinity of sickle cell erythrocytes. Also, proposed allosteric mechanisms for hemoglobin, based on S-nitrosation of beta-chain cysteine 93, raise the possibility of altering the pathophysiology of sickle cell disease by inhibiting polymerization or by increasing NO delivery to the tissue. We studied the effects of a 2-hour treatment, using varying concentrations of inhaled NO. Oxygen affinity, as measured by P(50), did not respond to inhaled NO, either in controls or in individuals with sickle cell disease. At baseline, the arterial and venous levels of nitrosylated hemoglobin were not significantly different, but NO inhalation led to a dose-dependent increase in mean nitrosylated hemoglobin, and at the highest dosage, a significant arterial-venous difference emerged. The levels of nitrosylated hemoglobin are too low to affect overall hemoglobin oxygen affinity, but augmented NO transport to the microvasculature seems a promising strategy for improving microvascular perfusion.
authors.affiliation: Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. mgladwin@nih.gov
authors.forename: M T
authors.initials: MT
authors.lastname: Gladwin
authors.forename: A N
authors.initials: AN
authors.lastname: Schechter
authors.forename: J H
authors.initials: JH
authors.lastname: Shelhamer
authors.forename: L K
authors.initials: LK
authors.lastname: Pannell
authors.forename: D A
authors.initials: DA
authors.lastname: Conway
authors.forename: B W
authors.initials: BW
authors.lastname: Hrinczenko
authors.forename: J S
authors.initials: JS
authors.lastname: Nichols
authors.forename: M E
authors.initials: ME
authors.lastname: Pease-Fye
authors.forename: C T
authors.initials: CT
authors.lastname: Noguchi
authors.forename: G P
authors.initials: GP
authors.lastname: Rodgers
authors.forename: F P
authors.initials: FP
authors.lastname: Ognibene
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood*; D044383:Black People; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006441:Hemoglobin A / Q000378:metabolism*; D006451:Hemoglobin, Sickle / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood*; D010108:Oxyhemoglobins / Q000378:metabolism*; D010313:Partial Pressure; D012016:Reference Values; D014481:United States; D044465:White People; D001741:Black or African American
chemical_list: D006451:Hemoglobin, Sickle; D010108:Oxyhemoglobins; D009569:Nitric Oxide; D006441:Hemoglobin A; D010100:Oxygen