NDLI: Ethanol attenuates peripheral NMDAR-mediated vascular oxidative stress and pressor response.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	McGee, Marie A. Abdel-Rahman, Abdel A.
Description	Country affiliation: United States Author Affiliation: McGee MA ( Department of Pharmacology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.); Abdel-Rahman AA ( Department of Pharmacology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA. Electronic address: abdelrahmana@ecu.edu.)
Abstract	There are no studies on the acute effect of ethanol on peripheral N-methyl-d-aspartate receptor (NMDAR)-mediated increases in reactive oxygen species (ROS) and blood pressure (BP). We tested the hypothesis that ethanol antagonism of peripheral NMDAR dampens systemic NMDA-evoked increases in vascular ROS and BP. We investigated the effect of ethanol (1 g/kg) on BP and heart rate (HR) responses elicited by systemic bolus (125-1000 µg/kg, intra-venous [i.v.]) or infused (180 µg/kg/min) NMDA in conscious male Sprague-Dawley rats. We also hypothesized that peripheral NMDAR blockade with DL-2-Amino-5-phosphonopentanoic acid (AP-5; 5 mg/kg, i.v.) uncovers an ethanol- (1 or 1.5 g/kg) evoked hypotensive response. Ethanol attenuated the peripheral NMDAR-mediated pressor and bradycardic responses caused by NMDA infusion, and ex vivo studies revealed parallel ethanol attenuation of peripheral NMDAR-mediated increases in vascular ROS. While ethanol (1 or 1.5 g/kg) alone had no effect on BP, the higher dose caused a hypotensive response in the presence of NMDAR blockade (AP-5). Blood ethanol concentrations were not statistically different in the groups that received ethanol alone or along with NMDA or AP-5. These findings are the first to demonstrate ethanol attenuation of peripheral NMDAR-mediated pressor response, and the uncovering of ethanol-evoked hypotension in the presence of peripheral NMDAR blockade.
File Format	HTM / HTML
ISSN	07418329
e-ISSN	18736823
DOI	10.1016/j.alcohol.2015.03.004
Journal	Alcohol
Issue Number	5
Volume Number	49
Language	English
Publisher	Elsevier
Publisher Date	2015-08-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Substance-Related Disorders Blood Pressure Drug Effects Ethanol Pharmacology Oxidative Stress Reactive Oxygen Species Blood Receptors, N-methyl-d-aspartate Agonists Antagonists & Inhibitors 2-amino-5-phosphonovalerate Animals Heart Rate N-methylaspartate Research Support, N.i.h., Extramural
Content Type	Text
Resource Type	Article
Subject	Neurology Medicine Behavioral Neuroscience Health (social science) Biochemistry Toxicology

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