Conversion of Nitroglycerin to Nitric Oxide in Microsomes of the Bovine Coronary Artery Smooth Muscle is Not Primarily Mediated by Glutathione-S-Transferases’

The pharmacological action of organic nitrate vasodilators [e.g., nitroglycerin (NTG)J is thought to be mediated through metabolic conversion to nitric oxide (NO); conversion leads to vasodilata-tion, whereas diminished conversion in chronic therapy may lead to pharmacological tolerance. The biochemical nature of this process, however, is poorly understood. Glutathione-S-transfer-ases (GST) have been shown to metabolize organic nitrates in the liver, but it is not known whether these enzymes are involved in this pharmacologically relevant process. We, therefore, com-pared the activities of conversion of NTG to NO vs. those of GST in microsomal suspensions of bovine coronary artery smooth muscle tissue. A classical GST substrate, 1-chloro-2,4-dinitrobenzene, inhibited NO production in microsomes, sug-gesting possible involvement of GST in organic nitrate activation