Nitric oxide metabolism in adults with cyanotic congenital heart disease.
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.
Han
Tae H
TH
Department of Chemical Engineering, University of California, Los Angeles, California, USA.
Perloff
Joseph K
JK
Liao
James C
JC
D000328:Adult; D016022:Case-Control Studies; D003490:Cyanosis / Q000097:blood* / Q000209:etiology; D005260:Female; D006442:Glycated Hemoglobin; D006330:Heart Defects, Congenital / Q000097:blood* / Q000150:complications; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008163:Luminescent Measurements; D008297:Male; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*
D006442:Glycated Hemoglobin; D006454:Hemoglobins; D009569:Nitric Oxide; C058377:hemoglobin A, glycosylated-nitric oxide complex; C008657:nitrosyl hemoglobin