Angiotensin (1-7) contributes to nitric oxide tonic inhibition of vasopressin release during hemorrhagic shock in acute ethanol intoxicated rodents

Acute ethanol intoxication (AEI) attenuates the arginine vasopressin (AVP) response to hemorrhage leading to impaired hemodynamic counter-regulation and accentuated hemodynamic stability. Previously we identified that the ethanol-induced impairment of circulating AVP concentrations in response to hemorrhage was the result of augmented central nitric oxide (NO) inhibition. The aim of the current study was to examine the mechanisms underlying ethanol-induced up-regulation of paraventricular nucleus (PVN) NO concentration. Angiotensin (ANG) (1-7) is an important mediator of NO production through activation of the Mas receptor. We hypothesized that Mas receptor inhibition would decrease central NO concentration and thus restore the rise in circulating AVP levels during hemorrhagic shock in AEI rats. Conscious male Sprague–Dawley rats (300–325g) received a 15h intra-gastric infusion of ethanol (2.5g/kg+300mg/kg/h) or dextrose prior to a fixed-pressure (~40mmHg) 60min hemorrhage. The Mas receptor antagonist A-779 was injected through an intracerebroventricular (ICV) cannula 15min prior to hemorrhage. PVN NOS activity and NO were significantly higher in AEI compared to DEX-treated controls at the completion of hemorrhage. ICV A-779 administration decreased NOS activity and NO concentration, partially restoring the rise in circulating AVP level at completion of hemorrhage in AEI rats. These results suggest that Mas receptor activation contributes to the NO-mediated inhibitory tone of AVP release in the ethanol-intoxicated hemorrhaged host.