Disturbances in nitric oxide/cyclic guanosine monophosphate system in SHR/NDmcr-cp rats, a model of metabolic syndrome
Disturbances in nitric oxide/cyclic guanosine monophosphate system in SHR/NDmcr-cp rats, a model of metabolic syndrome
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DOI：
10.1016/j.lfs.2005.06.029
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发表时间：
2006-02-09
期刊：
影响因子：
6.1
通讯作者：
Shinozuka, K
中科院分区：
文献类型：
--
作者：
Kagota, S;Yamaguchi, Y;Shinozuka, K
代谢综合征是一组代谢异常，包括高血压、高脂血症、高胰岛素血症、葡萄糖不耐受和肥胖。据报道，在此类与生活方式相关的疾病中，一氧化氮（NO）产生或生物活性受损会导致动脉粥样硬化性血管疾病的发生。因此，在本研究中，我们研究了代谢综合征模型 SHR/NDmcr-cp (cp/cp) 大鼠 (SHR-cp) 主动脉中 NO/环磷酸鸟苷 (cGMP) 系统的变化。在SHR-cp的主动脉中，与Wistar-Kyoto大鼠相比，乙酰胆碱诱导的内皮依赖性舒张和硝普钠诱导的内皮非依赖性舒张显着受损。此外，硝普钠诱导的可溶性鸟苷酸环化酶的蛋白质水平和cGMP水平显着降低。相反，乙酰胆碱诱导的内皮NO合酶蛋白水平和cGMP水平显着升高，血浆NO2+NO3水平也升高。血浆中脂质过氧化物的水平和主动脉中过氧化亚硝酸盐生物标志物3-硝基酪氨酸的含量显着增加。这些发现表明，在 SHR-cp 的主动脉中，尽管 NO 诱导的舒张反应受损，但内皮细胞产生的 NO 增加。一氧化氮生成的增加可能是对多种因素的补偿反应，包括氧化应激的增加。 (c) 2005 Elsevier Inc. 保留所有权利。
Metabolic syndrome is a cluster of metabolic abnormalities, including hypertension, hyperlipidemia, hyperinsulinemia, glucose intolerance and obesity. In such lifestyle-related diseases, impairment of nitric oxide (NO) production or bioactivity has been reported to lead to the development of atherogenic vascular diseases. Therefore, in the present study we investigated changes in the NO/cyclic guanosine monophosphate (cGMP) system in aortas of SHR/NDmcr-cp (cp/cp) rats (SHR-cp), a model of the metabolic syndrome. In aortas of SHR-cp, endothelium-dependent relaxations induced by acetylcholine and endothelium-independent relaxations induced by sodium nitroprusside were significantly impaired in comparison with Wistar-Kyoto rats. Furthermore, protein levels of soluble guanyly cyclase and cGMP levels induced by sodium nitroprusside were significantly decreased. In contrast, protein levels of endothelium NO synthase and cGMP levels induced by acetylcholine were significantly increased, and plasma NO2 plus NO3 levels were also increased. The levels of lipid peroxide in plasma and the contents of 3-nitrotyrosine, a biomarker of peroxynitrite, in aortas were markedly increased. These findings indicate that in the aortas of SHR-cp, NO production from the endothelium, is augmented, although the NO-induced relaxation response is impaired. Enhanced NO production may be a compensatory response to a variety of factors, including increases in oxidative stress. (c) 2005 Elsevier Inc. All rights reserved.