The nucleus tractus solitarii (NTS) is the primary integrative center for baroreflex. NTS not only integrates convergent information from peripheral baroreceptors and higher blood pressure (BP) control centers in CNS but itself is the site of substantial modulation. Our previous studies demonstrated that microinjection of nicotine into the NTS decrease BP and heart rate (HR), which indicates nicotine plays cardiovascular modulatory role in the NTS. However, the mechanisms how nicotine modulate cardiovascular functions in the NTS remained unclear. The aim of this study was to investigate the molecular mechanisms of nicotine-induced depressor and bradycardic effects in the NTS. Male anesthetized Wistar-Kyoto rats, with or without intra-NTS nitric oxide synthase (NOS) inhibitors or ionotropic glutamate receptor inhibitors pretreatment, received intra-NTS nicotine microinjection. BP and HR were monitored. Besides, NTS with/without nicotine microinjection were dissected and subjected to immunoblotting and nitric oxide (NO) analysis. Our results demonstrated that NO analysis study revealed intra-NTS NO production elevated after nicotine microinjection. The depressor and bradycardic effects of intra-NTS nicotine microinjection were diminished by pretreatment of calmodulin inhibitor (W7, 0.33 nmol), non-specific NOS inhibitor (L-NAME, 33 nmol) and eNOS specific inhibitor (L-NIO, 6 nmol). The cardiovascular effects of nicotine were also attenuated by NMDA receptor inhibitor (MK801, 1 nmol), not by non-NMDA receptor inhibitor (NBQX, 10 pmol). Immunoblotting and immunohistochemical studies did not revealed nicotine induced eNOSS1177 phosphorylation in NTS. Using MEK inhibitor, PD98059, and nNOS specific inhibitor,Vinyl-L-NIO and 7-NI, there were no effect on the depressor and bradycardic effects of intra-NTS nicotine microinjection, and the phosphorylation of AktT473 was not induced by nicotine. Therefore, our results indicate that nicotine-induced depressor and bradycardic responses maybe mediated through activating eNOS by calmodulin and stimulating glutamate release in the NTS.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0826109-175313 |
| Date | 26 August 2009 |
| Creators | Chen, Siang-ru |
| Contributors | Pei-Jung Lu, Ching-Jiunn Tseng, Chang, L.S., Ming-Hong Tai |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0826109-175313 |
| Rights | not_available, Copyright information available at source archive |
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