Methylmercury affects cerebrovascular reactivity to angiotensin II and acetylcholine via Rho-kinase and nitric oxide pathways in mice
Methylmercury affects cerebrovascular reactivity to angiotensin II and acetylcholine via Rho-kinase and nitric oxide pathways in mice
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DOI：
10.1016/j.lfs.2016.01.033
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发表时间：
2016-02-15
期刊：
影响因子：
6.1
通讯作者：
Miyamoto, Atsushi
中科院分区：
文献类型：
--
作者：
Islam, Md. Zahorul;Van Dao, Cuong;Miyamoto, Atsushi
目的：甲基汞 (MeHg) 暴露会增加患高血压和心血管疾病的风险。在本研究中，我们旨在探讨小鼠体内甲基汞暴露是否影响血压以及基底动脉对血管紧张素II（Ang II）和乙酰胆碱（ACh）的反应，血管紧张素II（Ang II）和乙酰胆碱（ACh）是脑血管自动调节的重要调节剂。主要方法：小鼠在饮用水中暴露于甲基汞（40 ppm）21天。通过间接尾套法测量清醒小鼠的血压。使用微器官浴系统对离体动脉对血管活性物质的反应进行功能研究。主要发现：在甲基汞治疗 2 周和 3 周后，收缩压和平均血压分别显着升高。在 MeHg 处理的小鼠中，Ang II 诱导的分离基底动脉收缩（通过 Rho 激酶激活介导）增加。乙酰胆碱诱导的松弛依赖于内皮细胞产生的一氧化氮，在甲基汞处理的小鼠中减少了。然而，在离体胸主动脉中未观察到血管对 Ang II 和 ACh 反应的改变。意义：这项研究表明，脑血管系统似乎对体内 MeHg 暴露特别敏感。我们的结果表明，体内 MeHg 分别通过增强 Rho 激酶活性和抑制 NO 生物利用度，升高血压并导致脑血管响应 Ang II 和 ACh 的反应性改变。 (C) 2016 Elsevier Inc. 保留所有权利。
Aims: Methylmercury (MeHg) exposure results in increased risk of hypertension and cardiovascular diseases. In this study, we aimed to investigate whether the in vivo exposure of MeHg in mice affects blood pressure and basilar arterial responses to angiotensin II (Ang II) and acetylcholine (ACh), which are important modulators of cerebrovascular autoregulation.Main methods: Mice were exposed to MeHg (40 ppm) in drinking water for 21 days. Blood pressure was measured in conscious mice by an indirect tail-cuff method. Functional studies of the isolated arteries' response to vasoactive substances were performed using a micro-organ-bath system.Key findings: Systolic and mean blood pressures were significantly increased after 2 and 3 weeks of treatment with MeHg, respectively. Ang II-induced contraction in an isolated basilar artery, which is mediated via Rho-kinase activation, was increased in MeHg-treated mice. ACh-induced relaxation, which is dependent on NO production from the endothelial cells, was decreased in MeHg-treated mice. However, alterations of vascular responses to Ang II and ACh were not observed in the isolated thoracic aorta.Significance: This study demonstrated that the cerebral vasculature appears to be particularly sensitive to in vivo exposure of MeHg. Our results suggest that in vivo MeHg increases blood pressure and causes alterations in the cerebrovascular reactivity in response to Ang II and ACh through enhancement of Rho-kinase activity and inhibition of NO bioavailability, respectively. (C) 2016 Elsevier Inc. All rights reserved.