Mechanisms of impaired vasopressin response in acute alcohol‐intoxicated hemorrhaged rats

Abstract

Acute alcohol intoxication (AAI) blunts the neuroendocrine (catecholamine and arginine vasopressin (AVP)) response to hemorrhagic shock (HS) resulting in impaired blood pressure recovery during fluid resuscitation. Central stimulation of cholinergic nicotinic receptors restores AVP responses in AAI+HS suggesting that AAI disrupts signaling mechanisms controlling AVP release. We hypothesize the AAI‐mediated inhibition of supraoptic (SON) and paraventricular (PVN) responsiveness is controlled by alterations in the balance between inhibitory nitric oxide (NO) and stimulatory angiotensin II (ANG II) signaling. Chronically‐catheterized, adult male Sprague‐Dawley rats (250–300g) received a primed‐constant (2.5g/kg + 0.3g/kg/h) 15h intragastric infusion of alcohol or isocaloric/isovolumic dextrose (DEX). AAI produced a significant (~30%) increase in NO levels in the PVN and SON and NO synthase activity in the SON as compared to DEX controls. AAI did not alter circulating ANG II, but showed significant attenuation of ANG II in response to HS. These results suggest that the mechanisms underlying the attenuation of AVP release during HS in AAI involve altered balance between NO and ANG II control of hypothalamic responses. We predict that central inhibition of NO or ANG II stimulation will restore AVP and will in turn improve hemodynamic recovery from HS in AAI. Supported by DOD PR‐054196 and NIAAA‐AA7577.