The mechanisms by which hypoxic red blood cells (RBCs) elicit regional and organ-specific changes in vascular tone and blood flow are poorly understood. In 3 June Advanced Online Nature Medicine Timothy McMahon and colleagues from Duke University Medical Center, Durham, North Carolina, show that RBCs use nitric oxide (NO) to respond to changes in oxygen tension with graded vasodilator and vasoconstrictor activity (Nat Med 2002, DOI:10.1038/nm718).

McMahon et al. measured arterial and venous blood levels of hemoglobin (Hb)–NO, determined the disposition of NO bound to Hb as a function of oxygen tension and correlated these findings with studies of model systems and of RBC bioactivity. They observed that binding of NO to the hemes (FeNO) and thiols (SNO) of the Hb molecule varied as a function of HbO2 saturation (FeO2). Moreover, RBC/SNO-mediated vasodilator activity was inversely proportional to FeO2 over a wide range,...

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