Gabapentin Reduces Blood Pressure and Heart Rate through the Nucleus Tractus Solitarii

Hsin-Hung Chen ； Yih-Do Li ； Pei-Wen Cheng ； Yi-Chien Fang ； Chi-Cheng Lai ； Ching-Jiunn Tseng ； Jun-Yen Pan ； Tung-Chen Yeh

《Acta Cardiologica Sinica》 35卷6期 (2019/11) Pp. 627-633

https://doi.org/10.6515/ACS.201911_35(6).20190429B

摘要

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(ω)-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.

關鍵字

Central cardiovascular regulation ； Gabapentin ； Nitric oxide synthase ； Nucleus tractus solitarii