Effect of Thiol Status on Nitric Oxide Metabolism in the Circulation (original) (raw)

1997, Archives of Biochemistry and Biophysics

To elucidate the dynamics of nitric oxide (NO) menance. tabolism 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 Endothelium-derived relaxing factor (EDRF) 2 has normal rats and animals that were treated with a loadbeen identified as nitric oxide (NO) and/or NO-related ing dose of GSH or L-buthionine-[S,R]-sulfoximine (BSO), a specific inhibitor of GSH synthesis. When in-metabolites (1, 2). NO is released not only from endocubated in vitro with 0.2 mM NOC7, an NO donor, NO-thelial cells but also from other types of cells which Hb levels increased rapidly, peaked at 10 min, and dehave NO synthase (3-7). Although the physiological creased thereafter with a half-life of 35 min in blood importance of NO has been extensively studied (8), samples from control, BSO-treated, or GSH-loaded anionly limited information is available on the in vivo mals. Levels of low-molecular-weight RSNO in plasma metabolism of NO. It has been well documented that samples from the three animal groups also increased the affinity of hemoglobin (Hb) for NO is 300,000 times transiently, peaked at 10 min, and decreased thereafgreater than for O 2 (9, 10); hence, NO rapidly reacts ter. However, the amount of RSNO formed in GSHwith Hb to form the NO-Hb adduct [NO-Fe(II)Hb]. loaded rat plasma was significantly greater than in Although a part of endogenously synthesized NO can control and BSO-treated animals. Plasma levels of NOx bind Hb, quantitative aspects of the formation and merapidly and similarly increased in all animal groups. tabolism of NO-Hb remain to be elucidated. NO and Intravenously injected NOC7 also generated NO-Hb its metabolite(s) also interact with thiol compounds in circulating erythrocytes. In control animals, blood (11, 12) to form RSNO (13). Rubanyi (14) reported that levels of NO-Hb increased maximally at 30 min and RSNO, such as the NO conjugates of cysteine and gludecreased thereafter with a half-life of 100 min. NOtathione, have EDRF-like function. Stamler et al. (12, Hb formed in the GSH-loaded group was significantly 15-17) reported that sulfhydryl groups of plasma prolower than in the control group. In contrast, the rate teins also form stable and biologically active NO adof NO-Hb formation was significantly higher with the ducts. Scharfstein et al. (18) demonstrated that the BSO-treated group than with the control group. Al-NO moiety bound to plasma protein thiols might be though NOC7 did not affect the plasma levels of lowtransferred to low-molecular-weight thiols. Recently, molecular-weight RSNO in plasma of both control and S-nitrosohemoglobin has been suggested to function BSO-treated groups, it significantly increased RSNO in the GSH-loaded group. Thirty minutes after admin-as a vasoactive regulator (19). RBC contain high conistration of NOC7, about 20% of the dose was recovered as plasma NOx in all animal groups. These results sug-2 Abbreviations used: EDRF, endothelium-derived relaxing factor; gested that GSH status in animals might affect the me-ESR, electron spin resonance; NOC7, [1-hydroxy-2-oxo-3-(N-methyltabolism of NO.