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Effective mechanisms in restoring blood pressure following hemorrhage
Author(s) -
Mathis Keisa W.,
Whitaker Annie M.,
Molina Patricia E.
Publication year - 2008
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.22.1_supplement.1227.16
Subject(s) - vasopressin , medicine , blood pressure , epinephrine , neostigmine , norepinephrine , endocrinology , anesthesia , hemodynamics , antagonist , dopamine , receptor
Acute alcohol intoxication (AAI) prior to injury and hemorrhage (HEM) accentuates hypotension and impairs blood pressure (BP) recovery during fluid resuscitation. The impaired hemodynamic counterregulation to HEM in AAI rodents is associated with attenuation of circulating levels of arginine vasopressin (AVP), epinephrine (Epi) and norepinephrine (NE). We hypothesize that restoration of the neuroendocrine response, either through central activation or systemically through vasopressor administration, will improve BP recovery and outcome from HEM during AAI. Parallel studies determined that intracerebroventricular (ICV) administration of neostigmine (acetylcholinesterase inhibitor) improves recovery of HEM‐ and AAI‐induced hypotension (A6488). The aim of the present study was to determine the efficacy of AVP in restoring the pressor response and to investigate the contribution of AVP in mediating the pressor response elicited by ICV neostigmine. A constant intravenous infusion of AVP (0.01 U/kg/min) was administered to catheterized, conscious male Sprague‐Dawley rats following a fixed‐pressure (40 mmHg) HEM. We observed improved pressor response to HEM in AVP‐treated animals. In a different set of animals, administration of a selective AVP receptor antagonist (V 1a ; 10μg/kg) blunted the neostigmine (1 μg) induced rise in BP. These results show improved BP recovery following HEM due to increased AVP activity produced by systemic administration and following central cholinergic activation. Furthermore, neostigmine produced a marked elevation in Epi (315±88%; P =0.001) and NE (89±29%, P=0.005) levels, suggesting that its pressor response cannot be solely attributed to enhanced AVP release. Whether similar effectiveness is achieved during AAI remains to be established and is focus of current investigation. Supported by DOD PR‐054196 and NIAAA‐AA7577.