Inhaled nitric oxide augments nitric oxide transport on sickle cell hemoglobin without affecting oxygen affinity

Nitric oxide (NO) inhalation has been reported to increase the oxygen affin ity of sickle cell erythrocytes. Also, proposed allosteric mechanisms for h emoglobin, based on S-nitrosation of P-chain cysteine 93, raise the possibi lty of altering the pathophysiology of sickle cell disease by inhibiting po lymerization or by increasing NO delivery to the tissue. We studied the eff ects of a 2-hour treatment, using varying concentrations of inhaled NO. Oxy gen 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 arte rial and venous levels of nitrosylated hemoglobin were not significantly di fferent, but NO inhalation led to a dose-dependent increase in mean nitrosy lated hemoglobin, and at the highest dosage, a significant arterial-venous difference emerged. The levels of nitrosylated hemoglobin are tao low to af fect overall hemoglobin oxygen affinity, but augmented NO transport to the microvasculature seems a promising strategy for improving microvascular per fusion.