Endothelial-derived
nitric oxide (NO) diffuses abluminally to regulate blood flow by activating
soluble guanylate cyclase in medial smooth muscle. However, a significant fraction of NO diffuses luminally, where the extremely high reaction rate with red blood cell
hemoglobin (Hb) effectively reduces
luminal concentration to zero. The
erythrocytosis of cyanotic
congenital heart disease has potentially opposing effects, namely, a reduction in medial smooth muscle NO bioavailability because of the increase in
luminal consumption of the molecule and, conversely, an increase in the elaboration of NO in response to the high endothelial shear stress of the erythrocytotic perfusate. NO metabolism in cyanotic
congenital heart disease is unknown. Accordingly, this study aimed to establish the metabolic fate of NO and to determine the degree to which its levels are altered. Blood samples from 25 nonfasting patients with cyanotic
congenital heart disease and 25 nonfasting normal controls were collected in Vacutainer tubes containing
citrate dextrose and in separate Vacutainer tubes containing a
solution that specifically preserves S-nitrosated Hb. Total NO species, plasma S-nitrosated
proteins,
iron nitrosyl Hb, and S-nitrosated Hb were quantified using chemiluminescence. In conclusion, a significant increase in plasma concentrations of NO metabolites and a modest increase in
iron nitrosyl Hb levels were found, suggesting increased
luminal consumption caused by
erythrocytosis and further suggesting that
hypoxemia might activate nonoxidative NO metabolic pathways and enhance tissue
oxygen delivery.