Gabapentin Reduces Blood Pressure and Heart Rate through the Nucleus Tractus Solitarii
Gabapentin Reduces Blood Pressure and Heart Rate through the Nucleus Tractus Solitarii
复制标题
DOI：
10.6515/acs.201911_35(6).20190429b
复制
发表时间：
2019-11-01
影响因子：
1.9
通讯作者：
Yeh, Tung-Chen
中科院分区：
文献类型：
--
作者：
Chen, Hsin-Hung;Li, Yih-Do;Yeh, Tung-Chen
背景：口服和静脉注射加巴喷丁可以显著降低高血压大鼠的血压。孤立束核（NTS）是中枢神经系统中心血管控制和其他自主神经功能的主要综合中枢。然而，加巴喷丁介导的NTS心血管效应的信号机制仍不清楚。我们研究了一氧化氮合酶（NOS）信号通路是否参与加巴喷丁介导的自发性高血压（SHR）大鼠NTS血压调节。方法：SHR大鼠10 ~ 12周龄用聚氨酯麻醉。通过股动脉导管监测动脉压和心率（HR）。对于立体定向nts内显微注射，髓质背表面通过有限开颅暴露。观察加巴喷丁单侧微注射NTS是否改变与剂量相关的血压和心率。然后，观察N(omega)-硝基- l -精氨酸甲酯（L-NAME）治疗前后NTS单侧微量注射加巴喷丁是否改变血压和心率。结果：单侧微注射加巴喷丁对SHR大鼠产生明显的剂量相关的抑制和心动过缓作用。加巴喷丁对心血管的影响因事先给予NOS抑制剂L-NAME而减弱。结论：加巴喷丁通过NOS信号调节SHR大鼠NTS中枢血压和HR控制。
Background: Oral and intravenous gabapentin can markedly attenuate blood pressure (BP) in hypertensive rats. The nucleus tractus solitarii (NTS) is the primary integrative center for cardiovascular control and other autonomic functions in the central nervous system. However, the signaling mechanisms involved in gabapentin-mediated cardiovascular effects in the NTS remain unclear. We investigated whether the nitric oxide synthase (NOS) signaling pathway was involved in gabapentin-mediated BP regulation in the NTS of spontaneously hypertensive (SHR) rats.Methods: SHR rats were anesthetized with urethane at age 10-12 weeks. Arterial pressure and heart rate (HR) were monitored through a femoral artery catheter. For stereotaxic intra-NTS microinjection, the dorsal surface of the medulla was exposed by limited craniotomy. We observed that unilateral microinjection of gabapentin into the NTS whether to change dose-related BP and HR. Then, unilateral microinjection of gabapentin into the NTS before and after N(omega)-nitro-L-arginine methyl ester (L-NAME) treatment whether to change blood pressure and heart rate.Results: Unilateral microinjection of gabapentin into the NTS produced prominent dose-related depressor and bradycardic effects in SHR rats. The cardiovascular effects of gabapentin were attenuated by the prior administration of the NOS inhibitor, L-NAME.Conclusions: Gabapentin modulated central BP and HR control in the NTS of SHR rats in this study through NOS signaling.