Biotransformation of glyceryl trinitrate to glyceryl dinitrate by human hemoglobin

The elimination of glyceryl trinitrate (GTN) by man is rapid and its clearance exceeds cardiac output. It is therefore clear that a variety of tissues in addition to liver are involved in the biotransformation of GTN. Incubation of GTN with the 25 000 X g supernatant fraction of lysed human erythrocytes resulted in a 39.6% +/- 5.5 (SD) elimination of GTN after 40 min. After pretreatment of the lysate supernatant fraction with carbon monoxide, GTN elimination was only 26% +/- 4.5. These data indicated that hemoglobin might be involved in GTN elimination. When purified hemoglobin was incubated with GTN, a 77.1% +/- 6.4 elimination of GTN was observed, accompanied by glyceryl dinitrate formation. The biotransformation of GTN was inhibited by pretreatment with carbon monoxide. The results indicate that the biotransformation of GTN by human erythrocytes is due, at least in part, to interaction with hemoglobin.