Interleukin-10 limits increased blood pressure and vascular RhoA/Rho-kinase signaling in angiotensin II-infused mice
Interleukin-10 limits increased blood pressure and vascular RhoA/Rho-kinase signaling in angiotensin II-infused mice
复制标题
DOI：
10.1016/j.lfs.2015.12.009
复制
发表时间：
2016-01-15
期刊：
影响因子：
6.1
通讯作者：
Giachini, Fernanda R.
中科院分区：
文献类型：
--
作者：
Lima, Victor V.;Zemse, Saiprasad M.;Giachini, Fernanda R.
目的：白细胞介素-10（IL-10）是一种多功能细胞因子，具有强效抗炎作用。我们假设IL-10限制了血管紧张素II（Ang II）高血压小鼠动脉中RhoA/Rho激酶信号传导和血管反应性的增加。主要方法：野生型（WT）和IL-10敲除（（-/-））小鼠输注Ang II（90 ng/min）14天。此外，WT小鼠输注Ang II并同时输注外源性IL-10（0.5 μ g/min，14天）。主动脉环被固定在一个myograph和浓度-反应曲线苯肾上腺素（PE）进行了评估。关键发现：血管紧张素II输注后，血压反应，但不是最大收缩PE，是更大的IL-10（-/-）小鼠，相比WT。与IL-10（-/-）高血压小鼠相比，Rho激酶抑制（Y-27632; 10 μ M）导致WT高血压小鼠PE诱导的收缩更明显减少。IL-10外源性输注可防止Ang II输注WT小鼠的血压升高。在输注Ang II的WT小鼠的主动脉中观察到的增强的PE收缩也被IL-10的外源性输注所阻止。此外，Rho-激酶抑制（Y-27632; 10 μ M）取消了这些groups.Significance之间的PE收缩反应的差异：这些结果表明，IL-10抵消了血管紧张素II以及与高血压相关的血管功能障碍，部分，调节RhoA-Rho激酶通路的升压活性。在高血压期间提高IL-10水平的策略可能会增强常规治疗提供的益处。(C)2015 Elsevier Inc. All rights reserved.
Aims: Interleukin-10 (IL-10) is a multi-functional cytokine with potent anti-inflammatory properties. We hypothesized that IL-10 limits increased RhoA/Rho-kinase signaling and vascular reactivity in arteries from angiotensin II (Ang II) hypertensive mice.Main methods: Wild type (WT) and IL-10 knockout ((-/-)) mice were infused with Ang II (90 ng/min) for 14 days. Additionally, WT mice were infused with Ang II and simultaneously infused with exogenous IL-10 (0.5 eta g/min, 14 days). Aortic rings were mounted in a myograph and concentration-response curve to phenylephrine (PE) were evaluated.Key findings: After Ang II infusion, blood pressure responses, but not maximal contraction to PE, was greater in IL-10(-/-) mice, compared to WT. Rho-kinase inhibition (Y-27632; 10 mu M) resulted in a more evident reduction of PE-induced contraction in WT hypertensive mice, when compared to IL-10(-/-) hypertensive mice. IL-10 exogenous infusion prevented the blood pressure increase in Ang II-infused WT mice. The augmented PE-contraction observed in aorta from WT mice infused with Ang II was also prevented by exogenous infusion of IL-10. Additionally, Rho-kinase inhibition (Y-27632; 10 mu M) abolished the differences in the contractile response to PE between these groups.Significance: These results demonstrate that IL-10 counteracts both the pressoric activity of Ang II as well as vascular dysfunction associated with hypertension, partially, modulating the RhoA-Rho kinase pathway. Strategies to enhance IL-10 levels during hypertension may enhance the benefits provided by regular treatments. (C) 2015 Elsevier Inc. All rights reserved.