Angiotensin II (Ang II) exerts diverse physiological actions in both peripheral and central nervous system. It has been demonstrated to implicate in central mechanisms leading to hypertension in the nucleus tractus solitarii (NTS) of rats, and mediated by the type-1 receptors (AT1R). Our previous studies already suggested that inhibition of NO synthesis in the NTS causes sustained hypertension. It was reported that the activity of Ang II was higher in the NTS of spontaneously hypertensive rat (SHR) and AT1R are colocalized in the neurons of the NTS, providing the local reactive oxygen species (ROS) production by Ang II. However, the signaling mechanisms of Ang II that induce hypertension remain uncertain. In the present study, we investigated the possible signal pathways involved in the cardiovascular regulation of Ang II in the NTS. Male SHR was treated with AT1R blocker, losartan (30 mg/kg/day) or superoxide dismutase (SOD) mimetic, tempol (1 mM/kg/day) for two weeks, systolic blood pressure was decreased significantly in losartan- or tempol-treated SHR. The NTS was excised for dihydroethidium (DHE) staining, NO analysis, immunoblotting and immunohistochemistry. Our results demonstrated that DHE staining revealed of ROS was much more in the NTS of SHR than in the NTS of wistar-Kyoto (WKY) rat. The ROS in the NTS of SHR was reduced by losartan. The NO content in the NTS of SHR was lower than WKY, while losartan and tempol could increase NO in the NTS of SHR. Immunoblotting and immunohistochemistry studies demonstrated that Ang II-induced hypertension inhibited neuronal NO synthase (nNOS), ERK and RSK phosphorylation levels in the NTS of SHR. These results suggest that Ang II induces ROS production in the NTS of SHR. In addition, the cardiovascular modulatory effects of Ang II in the NTS are accomplished by downregulation of ERK1/2-RSK phosphorylation levels and then nNOS level.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0806108-164040 |
| Date | 06 August 2008 |
| Creators | Cheng, Wen-han |
| Contributors | Pei-jung Lu, Ching-jiunn Tseng, Long-sen Chang, Yow-ling Shiue |
| 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-0806108-164040 |
| Rights | campus_withheld, Copyright information available at source archive |
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