DIRECT EVIDENCE FOR NITRIC-OXIDE FORMATION FROM GLYCERYL TRINITRATE DURING INCUBATION WITH INTACT BOVINE PULMONARY-ARTERY

It has been proposed that the mechanism of the vasodilator action of g lyceryl trinitrate (GTN) involves biotransformation to nitric oxide. A sensitive chemiluminescence method for nitric oxide determination was used to test this hypothesis. In four experiments, bovine pulmonary a rtery (BPA) was incubated with GTN (0.1 mM) in Kreb's solution (2 mL) containing 30 mM KCl, and in anaerobic conditions using 95% Ar - 5% CO 2, in a sealed micro-Fernbach flask (6.2-mL volume). After incubation for 2, 5, 10, or 20 min at 37-degrees-C, 400-mu-L aliquots of headspac e gas were removed and injected into a redox chemiluminescence detecto r. Nitric oxide formation was first measurable at 5 min (76 +/- 53 pmo l/g wet wt. BPA), and increased with incubation time (174 +/- 46 pmol/ g wet wt. PBA after 10 min and 310 +/- 67 pmol/g wet wt. BPA after 20 min). This is the first direct chemical measurement of nitric oxide fo rmation during interaction of GTN with vascular smooth muscle. These d ata support the concept that GTN is a nitrovasodilator prodrug acting via the formation of nitric oxide.