Participation of Hydrogen Sulfide and Oxidative Stress in Enhancement of Baroreflex Response by Methamphetamine in the Nucleus Tractus Solitarii in Rat
| Autor: | Chih-Han Chen, 陳芷涵 |
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| Rok vydání: | 2018 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 106 英文摘要 Methamphetamine (METH) is a potent psychostimulant abused worldwide, especially in Taiwan. METH causes detrimental effects on central nervous system (CNS) and cardiovascular functions. Previous studies indicate that METH is able to increase not only oxidative stress in brain but also S-adenosyl-l-methionine (SAM), an allosteric activator of cystathionine beta synthase (CBS), in serum. However, there is no evidence that METH increases the level of H2S through the generation of reactive oxygen species (ROS) and SAM. In addition, previous studies also indicate that both METH and H2S may enhance baroreflex response (BRR) via PI3K/Akt-nNOS-PKG signaling in the nucleus tractus solitarii (NTS). This study aimed at clarifying whether ROS and H2S mediates METH-induced BRR enhancement via PI3K/Akt-nNOS-PKG signaling in the NTS. Adult male Sprague-Dawley rats were used in this study. The result revealed that systemic administration or intra-NTS microinjection of N-acetylcysteine (NAC), TEMPOL, or CoQ10 significantly inhibited METH-enhanced BRR. To further clarify whether H2S was synthesized by CBS in the NTS, the expression of CBS was confirmed by Western blotting and immunohistochemistry staining. Also, intravenous injection or intra-NTS microinjection of AOAA, a CBS inhibitor, attenuated METH-induced enhancement of BRR. To examine METH-induced signaling pathway in the NTS, phosphorylation of neuronal nitric oxide (nNOS) was used as the index of nNOS signaling activation. The result showed that the METH-induced increase in nNOS phosphorylation could not be inhibited by intra-NTS microinjection of TEMPOL and METH. Furthermore, neither low nor high dose of METH injected into NTS enhanced BRR. In conclusion, these results suggested that METH doesn’t directly enhance BRR via PI3K/Akt-nNOS signaling pathway in the NTS, but METH-induced ROS and H2S may enhance BRR through other ways. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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