BIOACTIVATION OF NITROGLYCERIN IN VASCULAR SMOOTH-MUSCLE CELLS IS DIFFERENT FROM THAT IN NONVASCULAR TISSUE

The mechanism of biotransformation of nitroglycerin into the pharmacologically active radical nitric oxide (NO) or a related compound is still unclear. Different enzymes have been discussed to be involved in the bioactivation process. The effects of inhibition of glutathione-S-transferase and cytochrome P-450 enzymes were investigated on nitroglycerin-induced relaxation of bovine and porcine coronary arteries and on nitroglycerin-induced activation of guanylyl cyclase in cultivated porcine aortic smooth muscle cells. The glutathione-S-transferase inhibitor sulfobromophthalein had no effect on nitroglycerin-induced vascular relaxation, nor on nitroglycerin-induced elevation of cGMP levels in porcine coronary artery smooth muscle cells. The modulation of cytochrome P-450 activity by selective inhibitors as well as inducers did not alter the bioactivity of nitroglycerin in both systems. The data demonstrate that the isoenzymes of both enzyme families, which have been shown to be involved in the metabolism of nitroglycerin in different non-vascular tissues, do not play a role in bioactivation of nitroglycerin in the vascular system.