Increased Oxygen Dissociation by Nitric Oxide from RBC

Abstract

Endogenous carbon monoxide (CO), a product of heme oxygenase, is thought to share several biological actions with NO (Zhuo et al., 1993). Hemoglobin (Hb) tetramer in circulating erythrocytes traps the molecules so generated. CO increases the relative affinity of other heme sites for oxygen, thus shifting the remaining oxygen dissociation curve to the left, i.e., CO decreases oxygen (O₂) supply to tissues (Douglas et al. 1912). Exceedingly high concentration of NO also shifted the O₂ dissociation curve to the left (Kon et al., 1977). This may be because of the extremely high affinity of NO for Hb than CO. However, endogenous NO generated by stimuli (Green et al., 1981, Stuehr and Marietta, 1985, Hibbs et al., 1987) will not increase tissue hypoxia, because NO generated in vivo by cytokines or by nitrovasodilators (Kurz et al., 1993) is bound to the a subunit of eryth- rocyte Hb tetramer (Hb α-NO), composed of a and b subunits, and the Hb tetramer binding NO yields only less than 4% of total Hb tetramer in the circulating blood (Kosaka et al., 1994). Furthermore the present study shows that the small amount of NO decreases O₂ affinity of erythrocytes under low O₂ pressure (pO₂) and the effect is also observed in vivo.