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Inhaled nitric oxide augments nitric oxide transport on sickle cell hemoglobin without affecting oxygen affinity
Mark T. Gladwin, … , Griffin P. Rodgers, Frederick P. Ognibene
Mark T. Gladwin, … , Griffin P. Rodgers, Frederick P. Ognibene
Published October 1, 1999
Citation Information: J Clin Invest. 1999;104(7):937-945. https://doi.org/10.1172/JCI7637.
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Inhaled nitric oxide augments nitric oxide transport on sickle cell hemoglobin without affecting oxygen affinity

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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 β-chain cysteine 93, raise the possibilty 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 P50, 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

Mark T. Gladwin, Alan N. Schechter, James H. Shelhamer, Lewis K. Pannell, Deirdre A. Conway, Borys W. Hrinczenko, James S. Nichols, Margaret E. Pease-Fye, Constance T. Noguchi, Griffin P. Rodgers, Frederick P. Ognibene

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Figure 2

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Effect of inhaled 80 ppm inhaled NO on plasma NOX (nitrate and nitrite m...
Effect of inhaled 80 ppm inhaled NO on plasma NOX (nitrate and nitrite measured by the Griess reaction) and methemoglobin. (a) For 2 hours before NO inhalation, mean plasma levels of NOX in SS and AA individuals were 10 ± 8 μM and 12 ± 15 μM, respectively. After 2 hours of inhalation (hours 3 and 4; filled horizontal bar), mean levels rose significantly (P < 0.001) to 85 ± 8 μM in the SS individuals and 60 ± 15 μM in the AA individuals. After NO inhalation, there was a steady decrease in plasma NOX concentration. (b) During NO inhalation (hours 3 and 4; filled horizontal bar), mean methemoglobin levels rose from 0.3 ± 0.0% in the SS individuals and 0.24 ± 0.02% in the AA individuals to 1.2 ± 0.4% and 0.9 ± 0.09%, respectively (P = 0.001). After correcting for hemoglobin concentration, there was no difference in absolute methemoglobin values between AA and SS individuals. Values returned to baseline within 1–2 hours in all individuals.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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Referenced in 5 patents
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