title: Effect of thiol status on nitric oxide metabolism in the circulation.
abstract: To elucidate the dynamics of nitric oxide (NO) metabolism in the circulation and its relationship with glutathione metabolism, formation of nitrosylhemoglobin (NO-Hb), S-nitrosothiols (RSNO), and nitrite+nitrate (NOx) was determined in blood samples from normal rats and animals that were treated with a loading dose of GSH or L-buthionine-[S,R]-sulfoximine (BSO), a specific inhibitor of GSH synthesis. When incubated in vitro with 0.2 mM NOC7, an NO donor, NO-Hb levels increased rapidly, peaked at 10 min, and decreased thereafter with a half-life of 35 min in blood samples from control, BSO-treated, or GSH-loaded animals. Levels of low-molecular-weight RSNO in plasma samples from the three animal groups also increased transiently, peaked at 10 min, and decreased thereafter. However, the amount of RSNO formed in GSH-loaded rat plasma was significantly greater than in control and BSO-treated animals. Plasma levels of NOx rapidly and similarly increased in all animal groups. Intravenously injected NOC7 also generated NO-Hb in circulating erythrocytes. In control animals, blood levels of NO-Hb increased maximally at 30 min and decreased thereafter with a half-life of 100 min. NO-Hb formed in the GSH-loaded group was significantly lower than in the control group. In contrast, the rate of NO-Hb formation was significantly higher with the BSO-treated group than with the control group. Although NOC7 did not affect the plasma levels of low-molecular-weight RSNO in plasma of both control and BSO-treated groups, it significantly increased RSNO in the GSH-loaded group. Thirty minutes after administration of NOC7, about 20% of the dose was recovered as plasma NOx in all animal groups. These results suggested that GSH status in animals might affect the metabolism of NO.
authors.affiliation: Department of Biochemistry, Osaka City University Medical School, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Minamiyama
authors.forename: S
authors.initials: S
authors.lastname: Takemura
authors.forename: M
authors.initials: M
authors.lastname: Inoue
mesh_terms: D000818:Animals; D019328:Buthionine Sulfoximine / Q000097:blood / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D005978:Glutathione / Q000031:analogs & derivatives / Q000097:blood* / Q000494:pharmacology; D006454:Hemoglobins / Q000378:metabolism; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood*; D009573:Nitrites / Q000097:blood; D009603:Nitroso Compounds / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D026422:S-Nitrosoglutathione; D013438:Sulfhydryl Compounds / Q000097:blood*; D014226:Triazenes / Q000494:pharmacology
chemical_list: C100973:(1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-3-aminopropyl)-3-methyl-1-triazene; D006454:Hemoglobins; D009566:Nitrates; D009573:Nitrites; D009603:Nitroso Compounds; D013438:Sulfhydryl Compounds; D014226:Triazenes; C008657:nitrosyl hemoglobin; D009569:Nitric Oxide; D019328:Buthionine Sulfoximine; D026422:S-Nitrosoglutathione; D005978:Glutathione