NEURONAL NITRIC OXIDE SYNTHASE ACTIVATION IS INVOLVED IN INSULIN-MEDIATED CARDIOVASCULAR EFFECTS IN THE NUCLEUS TRACTUS SOLITARII OF RATS

NEURONAL NITRIC OXIDE SYNTHASE ACTIVATION IS INVOLVED IN INSULIN-MEDIATED CARDIOVASCULAR EFFECTS IN THE NUCLEUS TRACTUS SOLITARII OF RATS
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DOI:
10.1016/j.neuroscience.2008.12.048
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发表时间:
2009-03-17
期刊:
影响因子:
3.3
通讯作者:
Tseng, C. J.
Tseng, C. J.
中科院分区:
医学3区
文献类型:
--
作者:
Chiang, H. T.;Cheng, W. H.;Tseng, C. J.

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神经元型一氧化氮合酶(NNOS)广泛分布于中枢神经系统(CNS),被认为可以调节孤束核(NTS)的神经元活动。在这里,我们研究了nNOS的激活是否参与了胰岛素诱导的NTS的心血管反应。单侧NTS微量注射胰岛素(100IU/ml),分别于注射7-硝基吲唑(7-NI)(5pmoL)和N(5)-(1-亚氨基-3-丁烯基)-L-奥米辛(600pmo1)(600pmoL)前后评价心血管效应。将胰岛素或磷脂酰肌醇3-激酶(PI3K)抑制剂LY294002微量注入NTS后,用Western印迹和免疫组织化学方法检测nNOS的磷酸化水平。单侧NTS微量注射胰岛素对WKY大鼠有明显的降压和心动过缓作用。预先给予一氧化氮合酶抑制剂7-NI和乙烯-L-NIO可减轻胰岛素诱导的大鼠心血管反应。Western印迹分析显示nNOS表达显著增加(16.5+/-0.4倍;P
Neuronal nitric oxide synthases (nNOS) is distributed throughout the central nervous system (CNS) and has been proposed to modulate neuronal activity in the nucleus tractus solitarii (NTS). Here, we investigated whether the activation of nNOS is involved in insulin-induced cardiovascular responses in the NTS. Insulin (100 IU/ml) was unilaterally microinjected into the NTS, and the cardiovascular effects were evaluated before and after microinjection of the nNOS inhibitors 7-nitroindazole (7-NI) (5 pmol) and N(5)-(1-imino-3-butenyl)-l-omithine (vinyl-L-NIO) (600 pmol). Western blot and immunohistochemical analyses were performed to determine nNOS phosphorylation levels after insulin or phosphoinositide 3-kinase (PI3K) inhibitor LY294002 microinjection into the NTS. Unilateral microinjection of insulin into the NTS produced prominent depressor and bradycardic effects in WKY rats. Pretreatment with the nNOS inhibitors 7-NI and Vinyl-L-NIO attenuated the cardiovascular response evoked by insulin in Wistar-Kyoto (WKY) rats. Moreover, Western blot analysis showed a significant increase in nNOS (16.5 +/- 0.4-fold; P