Perivascular adipose tissue promotes vasoconstriction: The role of superoxide anion
Perivascular adipose tissue promotes vasoconstriction: The role of superoxide anion
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DOI：
10.1016/j.cardiores.2006.03.013
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发表时间：
2006-07-15
影响因子：
10.8
通讯作者：
Lee, Robert M. K. W.
中科院分区：
文献类型：
--
作者：
Gao, Yu-Jing;Takemori, Kumiko;Lee, Robert M. K. W.
目的：血管周围脂肪组织（PVAT）释放血管舒张因子。在这项研究中，我们研究了是否PVAT释放其他血管活性因子，以响应血管周围神经激活电场stimulation.Methods和结果：在Wistar-Kyoto大鼠，环上级肠系膜动脉（MA）与完整的PVAT（+）比环与PVAT删除（PVAT（-））显示出更大的收缩反应EFS。超氧化物歧化酶（SOD）对EFS引起的收缩反应的抑制作用在PVAT（+）MA中比在PVAT（-）MA中更明显。NAD（P）H氧化酶和环氧合酶抑制剂对EFS诱导的PVAT（+）MA收缩的抑制作用强于PVAT（-）MA。酪氨酸激酶抑制剂（tyrphostin A25）和MAPK/ERK抑制剂（U 0126）以浓度相关的方式减弱EFS诱导的PVAT（+）MA收缩，而这些抑制剂的非活性形式（tyrphostin A1和U 0124）不抑制这种反应。外源性超氧阴离子可增强对EFS和苯肾上腺素的收缩反应，抑制酪氨酸激酶和MAPK/ERK可减弱这种增强作用。EFS可增加PVAT和PVAT（+）/（-）MA的超氧阴离子生成，而抑制NAD（P）H氧化酶可减弱这种作用。结论：PVAT通过NAD（P）H氧化酶介导的超氧阴离子自由基的产生增强血管周围神经刺激引起的动脉收缩反应，这种增强作用与酪氨酸激酶和MAPK/ERK通路的激活有关。(c)2006年欧洲心脏病学会。出版社：Elsevier B.V版权所有。
Objectives: Recent studies have demonstrated that perivascular adipose tissue (PVAT) releases vascular relaxation factor(s). In this study, we examined if PVAT releases other vasoactive factors in response to perivascular nerve activation by electrical field stimulation (EFS).Methods and results: In Wistar-Kyoto rats, rings of superior mesenteric artery (MA) with intact PVAT (PVAT (+)) showed a greater contractile response to EFS than rings with PVAT removed (PVAT (-)). Superoxide dismutase (SOD) reduced the contractile response to EFS more in PVAT (+) MA than in PVAT (-) MA. Inhibitors of NAD(P)H oxidase and cyclooxygenase exerted a greater inhibition on EFS-induced contraction in PVAT (+) MA than in PVAT (-) MA. Inhibitors of tyrosine kinase (tyrphostin A25) and MAPK/ERK (U 0126) attenuated EFS-induced contraction in PVAT (+) MA in a concentration-related manner, while inactive forms of these inhibitors (tyrphostin A1 and U 0124) did not inhibit the response. Exogenous superoxide augmented the contractile response to EFS and to phenylephrine in PVAT (-) MA, and this augmentation was blunted by inhibition of tyrosine kinase and MAPK/ERK. EFS increased superoxide generation in isolated PVAT and PVAT (+)/(-) MA, which was attenuated by NAD(P)H oxidase inhibition. RTPCR showed the mRNA expression of p67(phox) subunit of NAD(P)H oxidase and immunohistochemical staining confirmed its localization in the adipocytes of PVAT.Conclusion: These results show that PVAT enhances the arterial contractile response to perivascular nerve stimulation through the production of superoxide mediated by NAD(P)H oxidase, and that this enhancement involves activation of tyrosine kinase and MAPK/ERK pathway. (c) 2006 European Society of Cardiology. Published by Elsevier B.V All rights reserved.