DISRUPTED NITRIC OXIDE CONTROL OF VASOPRESSIN RESPONSE TO HEMORRHAGE IN ACUTE ALCOHOL INTOXICATED RA TS.
Document Type
Presentation
Start Date
22-10-2010 10:15 AM
End Date
22-10-2010 10:30 AM
Description
Acute alcohol intoxication (AAI) impairs hemodynamic counter-regulation to hemorrhagic shock (HS) including greater hypotension to blood loss and impaired blood pressure recovery during hemorrhage and fluid resuscitation. This is associated with a blunted neuroendocrine response characterized by decreased circulating catecholamines and arginine vasopressin (AVP) which can be partially restored through central cholinergic stimulation, suggesting that AAI disrupts signaling mechanisms controlling AVP release. Under normovolumic and iso-osmotic conditions, AVP release is inhibited by nitric oxide (NO). AAI has been shown to increase NO levels in the paraventricular nucleus (PVN). We hypothesized that the attenuation of circulating AVP levels in AAl+HS is the result of increased central NO inhibition regulating AVP release. The aim of this study was to examine if removing the inhibition of NO will restore the AVP response to hemorrhage. Conscious, chronically catheterized male Sprague Dawley rats received a primedconstant 15 hour intra-gastric infusion of alcohol (ALC) (2.5g/kg + 300mg/kg/h BAL ~200mg/dl) or isocaloric/isovolumic dextrose (DEX). An intracerebroventricular (ICV) injection of either vehicle (sterile water) or the nitric oxide synthase (NOS) inhibitor, L-NAME; 50 μg/5μI, was administered 15 minutes prior to a fixed-pressure hemorrhage. The total blood volume removed to achieve a fixed-pressure of ~40mmHg was significantly (p<0.05) decreased in AAI; however, this was restored by administration of L-NAME. AAI increased NO levels (65%) in the PVN compared to DEX-treated controls. Administration of L-NAME significantly decreased NO levels in both DEXtreated (11.20±0.7 vs. 6.4±1.5 μM NO) and ALC-treated (31.6±1.2 vs. 7.0±1.8 μM NO) animals. Furthermore, L-NAME significantly decreased NOS activity in the PVN in both DEX-(0.60±0.16 vs. 0.25±0.02 μM NO/mg protein/min) and ALC-treated (0.70±0.08 vs. 0.25±0.04 μM NO/mg protein/min) animals. These results demonstrate that AAI increases NO inhibitory tone in the PVN and administration of L-NAME attenuates this response. Whether L-NAME improves the AVP response to hemorrhage remains to be elucidated. DOD PR-054196, NIAAA-AA7577.
Recommended Citation
Whitaker, Annie M.; Sulzer, J. K.; and Molina, P. E., "DISRUPTED NITRIC OXIDE CONTROL OF VASOPRESSIN RESPONSE TO HEMORRHAGE IN ACUTE ALCOHOL INTOXICATED RA TS." (2010). Dr. Joseph M. Moerschbaecher, III Graduate Research Day. 8.
https://digitalscholar.lsuhsc.edu/grad_rs/2010/presentation1/8
DISRUPTED NITRIC OXIDE CONTROL OF VASOPRESSIN RESPONSE TO HEMORRHAGE IN ACUTE ALCOHOL INTOXICATED RA TS.
Acute alcohol intoxication (AAI) impairs hemodynamic counter-regulation to hemorrhagic shock (HS) including greater hypotension to blood loss and impaired blood pressure recovery during hemorrhage and fluid resuscitation. This is associated with a blunted neuroendocrine response characterized by decreased circulating catecholamines and arginine vasopressin (AVP) which can be partially restored through central cholinergic stimulation, suggesting that AAI disrupts signaling mechanisms controlling AVP release. Under normovolumic and iso-osmotic conditions, AVP release is inhibited by nitric oxide (NO). AAI has been shown to increase NO levels in the paraventricular nucleus (PVN). We hypothesized that the attenuation of circulating AVP levels in AAl+HS is the result of increased central NO inhibition regulating AVP release. The aim of this study was to examine if removing the inhibition of NO will restore the AVP response to hemorrhage. Conscious, chronically catheterized male Sprague Dawley rats received a primedconstant 15 hour intra-gastric infusion of alcohol (ALC) (2.5g/kg + 300mg/kg/h BAL ~200mg/dl) or isocaloric/isovolumic dextrose (DEX). An intracerebroventricular (ICV) injection of either vehicle (sterile water) or the nitric oxide synthase (NOS) inhibitor, L-NAME; 50 μg/5μI, was administered 15 minutes prior to a fixed-pressure hemorrhage. The total blood volume removed to achieve a fixed-pressure of ~40mmHg was significantly (p<0.05) decreased in AAI; however, this was restored by administration of L-NAME. AAI increased NO levels (65%) in the PVN compared to DEX-treated controls. Administration of L-NAME significantly decreased NO levels in both DEXtreated (11.20±0.7 vs. 6.4±1.5 μM NO) and ALC-treated (31.6±1.2 vs. 7.0±1.8 μM NO) animals. Furthermore, L-NAME significantly decreased NOS activity in the PVN in both DEX-(0.60±0.16 vs. 0.25±0.02 μM NO/mg protein/min) and ALC-treated (0.70±0.08 vs. 0.25±0.04 μM NO/mg protein/min) animals. These results demonstrate that AAI increases NO inhibitory tone in the PVN and administration of L-NAME attenuates this response. Whether L-NAME improves the AVP response to hemorrhage remains to be elucidated. DOD PR-054196, NIAAA-AA7577.