Augmented central nitric oxide production inhibits vasopressin release during hemorrhage in acute alcohol-intoxicated rodents

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 301; no. 5; pp. R1529 - R1539
• Main Authors: Whitaker, Annie M, Sulzer, Jesse K, Molina, Patricia E
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.11.2011
• Subjects: Alcohol; Alcoholic Intoxication - blood; Alcoholic Intoxication - complications; Alcoholic Intoxication - metabolism; Alcoholic Intoxication - physiopathology; Animals; Arginine Vasopressin - metabolism; Blood Pressure; Blood Volume; Disease Models, Animal; Down-Regulation; Enzyme Inhibitors - pharmacology; Hemorrhage; Hemorrhage - blood; Hemorrhage - complications; Hemorrhage - metabolism; Hemorrhage - physiopathology; Hormones; Male; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - metabolism; Osmolar Concentration; Paraventricular Hypothalamic Nucleus - drug effects; Paraventricular Hypothalamic Nucleus - metabolism; Rats; Rats, Sprague-Dawley; Rodents; Signal Transduction; Supraoptic Nucleus - metabolism; Time Factors; Up-Regulation
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00035.2011

Acute alcohol intoxication (AAI) attenuates the AVP response to hemorrhage, contributing to impaired hemodynamic counter-regulation. This can be restored by central cholinergic stimulation, implicating disrupted signaling regulating AVP release. AVP is released in response to hemorrhage and hyperosmolality. Studies have demonstrated nitric oxide (NO) to play an inhibitory role on AVP release. AAI has been shown to increase NO content in the paraventricular nucleus. We hypothesized that the attenuated AVP response to hemorrhage during AAI is the result of increased central NO inhibition. In addition, we predicted that the increased NO tone during AAI would impair the AVP response to hyperosmolality. Conscious male Sprague-Dawley rats (300-325 g) received a 15-h intragastric infusion of alcohol (2.5 g/kg + 300 mg·kg(-1)·h(-1)) or dextrose prior to a 60-min fixed-pressure hemorrhage (∼40 mmHg) or 5% hypertonic saline infusion (0.05 ml·kg(-1)·min(-1)). AAI attenuated the AVP response to hemorrhage, which was associated with increased paraventricular NO content. In contrast, AAI did not impair the AVP response to hyperosmolality. This was accompanied by decreased paraventricular NO content. To confirm the role of NO in the alcohol-induced inhibition of AVP release during hemorrhage, the nitric oxide synthase inhibitor, nitro-l-arginine methyl ester (l-NAME; 250 μg/5 μl), was administered centrally prior to hemorrhage. l-NAME did not further increase AVP levels during hemorrhage in dextrose-treated animals; however, it restored the AVP response during AAI. These results indicate that AAI impairs the AVP response to hemorrhage, while not affecting the response to hyperosmolality. Furthermore, these data demonstrate that the attenuated AVP response to hemorrhage is the result of augmented central NO inhibition.