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Involvement of NMDA Receptors, Nitric Oxide, and GABA in Rostral Ventrolateral Medulla in Acute Ethanol-Induced

Hsuan Lo¹, Hsun-Hsun Lin², Jun-Kai Chen¹

¹Master and Ph.D. Programs in Pharmacology and Toxicology, School of Medicine, Tzu Chi University, Hualien, Taiwan.

Alcoholism, Clinical and Experimental Research

|May 31, 2018

Abstract

Background:

Consumption of ethanol (EtOH) (alcohol) has many effects on physiological functions, particularly those in the central nervous system (CNS) and cardiovascular system. Acute excessive intake of EtOH (alcohol intoxication) may cause hypotension and tachycardia. In this study, we examined the mechanistic involvement of glutamatergic N-methyl-d-aspartate (NMDA) receptors, nitric oxide (NO), and γ-aminobutyric acid (GABA) pathways in the CNS in acute EtOH-induced cardiovascular effects.

Methods:

EtOH was administered by intraperitoneal (IP) injection in Sprague-Dawley rats. The blood pressure (BP) and heart rate (HR) were measured in conscious and in urethane-anesthetized rats. Inhibitors were applied by intracerebroventricular (ICV) injection or by microinjection into rostral ventrolateral medulla (RVLM). Microdialysis was used to determine the level of glutamate, NO, and GABA in the RVLM.

Results:

IP injection of EtOH (3.2 g/kg) caused a significant decrease in BP in conscious and anesthetized rats and a late increase in HR in conscious rats. The cardiovascular effects of EtOH were significantly attenuated by ICV or by RVLM post treatment with ketamine (an NMDA receptor antagonist), N5-(nitroamidino)-L-2,5-diaminopentanoic acid (L-NNA; a NO synthase inhibitor), or bicuculline (a GABA receptor antagonist). EtOH caused an increase in the level of glutamate, NO, and GABA in the RVLM during the hypotensive responses. RVLM posttreatment with ketamine blocked the increase in NO and GABA levels; post treatment with L-NNA blocked the increase in GABA level.

Conclusions:

Our results indicate that EtOH augmentation of glutamatergic NMDA receptors/NO/GABA pathways in the RVLM may participate in the hypotensive effects induced by acute administration of EtOH.

Keywords:

GABA Alcohol Cardiovascular Response NMDA Receptors Nitric Oxide

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