Buthionine sulfoximine causes endothelium dependent hyper-relaxation and hypoadiponectinemia
Buthionine sulfoximine causes endothelium dependent hyper-relaxation and hypoadiponectinemia
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DOI：
10.1016/j.lfs.2006.11.012
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发表时间：
2007-02-06
期刊：
影响因子：
6.1
通讯作者：
Hattori, Yoshiyuki
中科院分区：
文献类型：
--
作者：
Iwata, Chigusa;Wang, Xi;Hattori, Yoshiyuki
已经观察到氧化应激、内皮功能障碍和低脂联素血症之间存在密切关系。本研究旨在调查通过丁硫氨酸亚砜亚胺 (BSO) 给药消除谷胱甘肽如何影响大鼠的内皮功能和脂联素水平。与对照大鼠相比，BSO 治疗大鼠的乙酰胆碱 (Ach) 诱导的血管舒张作用显着增强。 L-NAME 完全消除了这一点，并且在没有内皮的主动脉中没有观察到 Ach 诱导的血管舒张。这些结果表明，BSO 治疗大鼠中 Ach 诱导的主动脉过度松弛完全依赖于内皮细胞的存在，并由 eNOS 活性的变化介导。过氧化氢酶显着抑制了 Ach 的这种松弛，并且在 BSO 处理的大鼠中没有观察到过氧化氢酶对硝普钠诱导的无内皮主动脉松弛的影响。因此，BSO 治疗大鼠的主动脉过度松弛可能是由 H2O2 以及内皮细胞通过 eNOS 依赖性机制产生的 NO 引起的。在 BSO 治疗的大鼠中观察到低脂联素血症和脂肪组织中脂联素 mRNA 水平降低。 BSO 治疗的大鼠主动脉中 eNOS 和 SOD（SOD-1 和 SOD-2）的蛋白表达增加，血浆 NOx 水平降低。我们的结果表明，BSO 诱导的氧化应激通过产生 H2O2 导致 eNOS 解偶联和过度松弛，而 BSO 诱导的氧化应激可能通过增加脂肪组织中 H2O2 的产生而导致低脂联素血症。 (c) 2006 Elsevier Inc. 保留所有权利。
A close relationship between oxidative stress, endothelial dysfunction, and hypoadiponectinemia has been observed. The present study was performed to investigate how glutathione depletion via buthionine sulfoximine (BSO) administration affects endothelial function and adiponectin levels in rats. Acetylcholine (Ach)-induced vasodilation was significantly enhanced in BSO-treated rats, compared with control rats. This was completely abolished by L-NAME, and Ach-induced vasodilation was not observed in the aorta without endothelium. These results suggest that Ach-induced hyper-relaxation of the aorta in BSO-treated rats is completely dependent on the presence of endothelium and mediated by changes in eNOS activity. Catalase significantly inhibited this relaxation to Ach and no effect of catalase on sodium nitroprusside-induced relaxation of the aorta without endothelium was observed in BSO-treated rats. Thus, hyper-relaxation of the aorta in BSO-treated rats is likely caused by H2O2 in addition to NO produced by the endothelium via an eNOS-dependent mechanism. Hypoadiponectinemia and decreased levels of adiponectin mRNA in adipose tissue were observed in BSO-treated rats. Protein expression of eNOS and SODs (SOD-1 and SOD-2) in the aorta was increased and plasma NOx levels were decreased in BSO-treated rats. Our results suggest that oxidative stress induced by BSO causes eNOS uncoupling and hyper-relaxation by producing H2O2, and that BSO-induced oxidative stress causes hypoadiponectinemia, probably by increasing H2O2 production in adipose tissue. (c) 2006 Elsevier Inc. All rights reserved.