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

• Ethanol attenuated systemic NMDA-induced pressor responses.
• Prior NMDAR blockade uncovered ethanol-evoked hypotensive response.
• AP-5 had no effect on ethanol induction of vascular ROS levels.

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.