Nitroglycerin and isosorbide dinitrate stimulation of glutathione disulfide efflux from perfused rat liver.

Hill KE, Ziegler DM, Konz KH, Haap M, Hunt RW, Burk RF
Biochem Pharmacol. 1989 38 (21): 3807-10

PMID: 2512927 · DOI:10.1016/0006-2952(89)90589-3

Nitroglycerin (GTN) and isosorbide dinitrate (ISD) are metabolized by glutathione S-transferase to nitrite with production of GSSG from GSH. Infusion of organic nitrates into perfused rat liver led to efflux of GSSG in the bile and nitrite in the perfusate. Biliary GSSG increased more rapidly than did nitrite release as GTN infusion rate was increased, indicating that GSSG reducing capacity was being exceeded. Rapid GTN-induced oxidation of GSH may be the mechanism of tissue GSH depletion by GTN and other alkylnitrates. Such depletion of glutathione may reduce nitrite production from organic nitrates and underlie tolerance to these drugs.

MeSH Terms (14)

Animals Bile Biomarkers Glutathione Glutathione Disulfide Isosorbide Dinitrate L-Lactate Dehydrogenase Liver Male Nitroglycerin Oxidation-Reduction Perfusion Rats Rats, Inbred Strains

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