title: Ethanol attenuates peripheral NMDAR-mediated vascular oxidative stress and pressor response.
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.
authors.affiliation: Department of Pharmacology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
authors.forename: Marie A
authors.initials: MA
authors.lastname: McGee
authors.affiliation: Department of Pharmacology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA. Electronic address: abdelrahmana@ecu.edu.
authors.forename: Abdel A
authors.initials: AA
authors.lastname: Abdel-Rahman
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000097:blood*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000037:antagonists & inhibitors*
chemical_list: D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate
keywords: AP-5; Blood pressure; Ethanol; NO; Oxidative stress; Peripheral NMDAR