Effects of chronic N-acetylcysteine treatment on the actions of peroxynitrite on aortic vascular reactivity in hypertensive rats
Effects of chronic N-acetylcysteine treatment on the actions of peroxynitrite on aortic vascular reactivity in hypertensive rats
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DOI：
10.1097/00004872-200107000-00008
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发表时间：
2001-07-01
影响因子：
4.9
通讯作者：
de Champlain, J
中科院分区：
文献类型：
--
作者：
Cabassi, A;Dumont, EC;de Champlain, J
研究背景过氧化亚硝酸盐（ONOO-）是超氧阴离子和一氧化氮的产物，可能参与高血压血管病变的发生。目的探讨ONOO-对内皮依赖性和非内皮依赖性主动脉血管反应性、氧化还原型谷胱甘肽平衡的影响（GSSG/GSH）、丙二醛主动脉含量和3-硝基酪氨酸（3-NT）的形成，3-NT是ONOO-的稳定标志物，结果NAC仅能降低SHR的心率和收缩压，但对舒张压无明显影响。它还改善了SHR的内皮依赖性主动脉舒张，但在暴露于ONOO-后没有。内皮依赖性和独立的主动脉舒张功能显着受损ONOO-在这两种品系的大鼠。NAG部分保护SHR对抗ONOO诱导的内皮非依赖性舒张减少。SHR主动脉GSSG/GSH比值和丙二醛均高于WKY大鼠，ONOO-暴露后SHR的升高幅度更大。NAG能降低ONOO-染毒前后两种品系大鼠的GSSG/GSH和丙二醛含量。3-NT的浓度，这是在两个品系的大鼠在基础条件下相似，是在SHR比WKY大鼠后，除了ONOO-，减少只有NAG处理的SNR.Conclusions这些研究结果表明，增加的脆弱性SHR动脉ONOO-的影响相比，WKY大鼠。NAG对SHR收缩压、心率、主动脉内皮功能、ONOO-诱导的内皮非依赖性舒张功能障碍、主动脉GSSG/GSH平衡、丙二醛含量和3-NT形成的选择性改善表明，长期给予NAG可能对SHR高血压模型的主动脉血管功能障碍具有保护作用。(C)2001年利平科特威廉姆斯&威尔金斯。
Background Peroxynitrite (ONOO-), the product of superoxide and nitric oxide, seems to be involved in vascular alterations in hypertension.Objectives To evaluate the effects of ONOO- on endothelium-dependent and independent aortic vascular responsiveness, oxidized/reduced glutathione balance (GSSG/GSH), malondialdehyde aortic content, and the formation of 3-nitrotyrosine (3-NT), a stable marker of ONOO-, in N-acetylcysteine (NAC)-treated normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR).Results In SHR only, NAC significantly reduced heart rate and systolic, but not diastolic, blood pressure. It also improved endothelium-dependent aortic relaxation in SHR, but not after exposure to ONOO-. Endothelium-dependent and independent aortic relaxations were markedly impaired by ONOO- in both strains of rat. NAG partially protected SHR against the ONOO--induced reduction in endothelium-independent relaxation. Aortic GSSG/GSH ratio and malondialdehyde, which were higher in SHR than in WKY rats, showed a greater increase in SHR after exposure to ONOO-. NAG decreased GSSG/GSH and malondialdehyde in both strains of rat before and after exposure to ONOO-. The 3-NT concentration, which was similar in both strains of rat under basal conditions, was greater in SHR than in WKY rats after the addition of ONOO-, with a reduction only in NAG-treated SNR.Conclusions These findings suggest an increased vulnerability of SHR aortas to the effects of ONOO- as compared with those of WKY rats. The selective improvements produced by NAG, in systolic arterial pressure, heart rate, aortic endothelial function, ONOO--induced impairment of endothelium-independent relaxation, aortic GSSG/GSH balance, malondialdehyde content and 3-NT formation in SHR suggest that chronic administration of NAG may have a protective effect against aortic vascular dysfunction in the SHR model of hypertension. (C) 2001 Lippincott Williams & Wilkins.