Neuronal Nitric Oxide Synthase Activation Is Involved in Insulin-Mediated Cardiovascular Effects in the Nucleus Tractus Solitarii of Rats
| Autor: | Pei Jung Lu, Michael Hsiao, Yu-Chou Tseng, Wen Han Cheng, Ching-Jiunn Tseng, H. T. Chiang, Jui-Ling Wang, H. N. Huang, Wan-Chen Lo |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Ornithine inorganic chemicals medicine.medical_specialty Indazoles Microinjections Morpholines medicine.medical_treatment Blood Pressure Nitric Oxide Synthase Type I Rats Inbred WKY Gene Expression Regulation Enzymologic chemistry.chemical_compound Heart Rate Internal medicine Solitary Nucleus medicine Animals Immunoprecipitation Insulin Drug Interactions LY294002 Enzyme Inhibitors Protein kinase B Microinjection Analysis of Variance Dose-Response Relationship Drug biology Chemistry Kinase General Neuroscience Solitary nucleus Rats Enzyme Activation Nitric oxide synthase Insulin receptor Endocrinology nervous system Chromones cardiovascular system biology.protein |
| Zdroj: | Neuroscience. 159:727-734 |
| ISSN: | 0306-4522 |
| DOI: | 10.1016/j.neuroscience.2008.12.048 |
| Popis: | 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- ornithine (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 n =4) phosphorylation after insulin injection, whereas the PI3K inhibitor LY294002 abolished the insulin-induced effects. In situ nNOS phosphorylation was found to be increased in the NTS after insulin injection. Furthermore, co-immunoprecipitation assay showed Akt and nNOS can bind to each other as detected by phospho-Akt S473 and phospho-nNOS S1416 antibodies. In vitro kinase assay showed insulin activated Akt can directly phosphorylate nNOS S1416 . These results demonstrated that nNOS may couple with the activation of the insulin receptor, via the liberation of NO, in order to participate in central cardiovascular regulation of WKY rats. |
| Databáze: | OpenAIRE |
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