Biotransformation of glyceryl trinitrate by blood platelets as compared to vascular smooth muscle cells

The present study investigated the metabolism of glyceryl trinitrate by washed human platelets as compared to that by rat vascular smooth muscle cells. Possible changes in metabolism after induction of nitrate tolerance were also studied in both systems. Incubation of the cells with glyceryl trinitrate (0.1 mM) resulted in a time-dependent release of nitrite (NO2-) amounting to 6.30 +/- 0.63 nmol mg protein-1 h-1 in vascular smooth muscle cells and 0.61 +/- 0.08 nmol mg protein-1 h-1 for platelets, respectively. The nitric oxide (NO) scavenger, oxyhemoglobin (10 microM), significantly reduced NO2- generation in both cell types studied. Nitrate tolerance was induced by incubation of the cells with glyceryl trinitrate (2 mM) for 2 h. In tolerant vascular smooth muscle cells as well as in tolerant platelets, NO2- release was significantly reduced. The inhibitory capacity of glyceryl trinitrate on ADP (6 microM)-induced platelet aggregation and on intracellular Ca2+ signals was significantly reduced in tolerant platelets. The data show a direct metabolism of glyceryl trinitrate by human blood platelets which is subject to a type of tolerance development similar to that in vascular smooth muscle cells.