Hsin-Hung Chen1,2, Yih-Do Li3, Pei-Wen Cheng1,2, Yi-Chien Fang3, Chi-Cheng Lai4, Ching-Jiunn Tseng1, Jun-Yen Pan5,6, Tung-Chen Yeh7,8. 1. Department of Medical Education and Research. 2. Yuh-Ing Junior College of Health Care & Management. 3. Department of Laboratory Medicine, Zuoying Branch of Kaohsiung Armed Forces General Hospital. 4. Cardiology, Kaohsiung Municipal United Hospital. 5. Division of Cardiovascular Surgery, Department of Surgery. 6. Department of Nursing, Shu-Zen Junior College of Medicine and Management, Kaohsiung. 7. Department of Internal Medicine, Division of Cardiology, Kaohsiung Veterans General Hospital. 8. Department of Nursing, Chung Hwa University of Medical Technology, Tainan, Taiwan.
Abstract
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.
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.
Authors: Matthew Ho; Maria Moscvin; Soon Khai Low; Benjamin Evans; Sara Close; Robert Schlossman; Jacob Laubach; Claudia Paba Prada; Brett Glotzbecker; Paul G Richardson; Giada Bianchi Journal: Leuk Lymphoma Date: 2022-06-14