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Involvement of NMDA Receptors, Nitric Oxide, and GABA in Rostral Ventrolateral Medulla in Acute Ethanol‐Induced Cardiovascular Responses in Rats
Author(s) -
Lo Hsuan,
Lin HsunHsun,
Chen JunKai,
Situmorang Jiro Hasegawa,
Lai ChihChia
Publication year - 2018
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13800
Subject(s) - rostral ventrolateral medulla , nmda receptor , glutamate receptor , microinjection , glutamatergic , endocrinology , medicine , nitric oxide , medulla oblongata , pharmacology , chemistry , bicuculline , microdialysis , gabaa receptor , receptor , central nervous system
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.