NO metabolites accumulate in erythrocytes in proportion to carbon dioxide and bicarbonate concentration

It is not known whether the ratio between the concentrations of NO metaboli tes (NOx) in plasma (pNOx) and in erythrocytes (eNOx) is constant or correl ates with chemical parameters of the blood. We measured pH, PO2, and PCO2 a nd calculated bicarbonate concentration in 19 blood samples from the aorta, coronary sinus, and leg veins of 7 dogs. Erythrocytes were then separated by centrifugation and lysed with distilled water, and the lysate was ultraf iltered with a molecular cutoff of 50 kDa to remove the hemoglobin. NOx wer e measured in plasma and in the ultrafiltrate. NOx concentration was higher in erythrocytes, with eNOx/pNOx ranging from 4.38 to 14.60. Linear and sig nificant correlations were found between the natural logarithm of eNOx/pNOx and PCO2 (r = 0.70, P < 0.001) or bicarbonate concentration (r = 0.72, P < 0.001). These results demonstrate, for the first time, that plasma NOx can not be considered as a constant fraction of the total NOx in blood but vari es dramatically in proportion to the CO2/bicarbonate concentration. To prev ent an underestimation of venous-arterial difference of NOx across organs, NOx should be measured in whole blood.