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Angiotensin 1–7 Contributes to Disrupted Nitric Oxide control of Vasopressin Response to Hemorrhage during Acute Alcohol Intoxication
Author(s) -
Whitaker Annie M.,
Molina Patricia E.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1132.12
Subject(s) - vasopressin , endocrinology , medicine , nitric oxide , angiotensin ii , antagonist , arginine , chemistry , downregulation and upregulation , receptor , renin–angiotensin system , alcohol , blood pressure , amino acid , biochemistry , gene
Acute alcohol intoxication (AAI) impairs hemodynamic counterregulation and blunts the arginine vasopressin (AVP) response to hemorrhagic shock (HS). We have demonstrated that AAI disrupts signaling mechanisms controlling AVP release through upregulation of paraventricular (PVN) nitric oxide (NO) and attenuated angiotensin (ANG) II response to HS. We hypothesized that AAI may also enhance ANG Converting Enzyme (ACE) 2 activity promoting the conversion of ANG II to the NO‐stimulating peptide ANG (1–7) further contributing to AAI‐induced suppression of AVP release. Male Sprague‐Dawley rats (250–300g) received a primed (2.5g/kg + 0.3g/kg/h) 15h intragastric infusion of alcohol or dextrose (DEX) prior to fixed‐pressure (40 mmHg) HS. AAI increased PVN ACE2 activity (41%) compared to DEX+HS. The contribution of ANG (1–7) to the AAI‐induced increase in PVN NO, was demonstrated by central administration of the Mas receptor antagonist A‐779 prior to HS. AAI increased NOS activity (30%) and NO levels (40%) in the PVN compared to DEX controls. Administration of A‐779 decreased NOS activity (66%), NO levels (27%; p=NS) and partially restored AVP levels (20%) in AAI‐treated animals. These results suggest that increased hypothalamic Mas receptor activation partially contributes to the alcohol‐induced disruption of NO control of AVP release during HS. DOD PR‐054196, NI7577, APS Porter Fellowship.