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Cerebral aquaporins in an acute mountain sickness model ‐ response to global hypoxia in vivo
Author(s) -
Bernhardtsen Tine,
Gjerris Flemming,
Olsen Niels Vidiendal,
Jonassen Thomas EN
Publication year - 2006
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.20.4.a732-c
Subject(s) - acetazolamide , downregulation and upregulation , hypoxia (environmental) , medicine , in vivo , choroid plexus , cerebral edema , aquaporin 4 , endocrinology , anesthesia , aquaporin 1 , pharmacology , chemistry , central nervous system , biology , oxygen , biochemistry , microbiology and biotechnology , organic chemistry , water channel , mechanical engineering , engineering , inlet , gene
Acute mountain sickness (AMS) is a condition with global tissue hypoxia associated with symptoms of increased intracranial pressure. Acetazolamide prophylaxis is used in AMS and has reportedly beneficial effects on cerebral symptoms, underlying mechanism not yet elucidated. The aim of the present study was to examine protein levels of cerebral aquaporins (AQPs) in an experimental model of acute global hypoxia and to study the effect of acetazolamide on AQP1. Male Wistar rats were subjected to normobaric hypoxia of 7% oxygen for 48 hours which caused ~10 % weight loss and dehydration. Time matched and thirsted rats were therefore used as controls. Separate series were injected with acetazolamide i.p.15mg/kg/day. Microvascular leakage was demonstrated visualizing extravasated endogenous albumin by immunohistochemistry. Western blotting on whole brain homogenates revealed a 28% upregulation of AQP4 (p<0.005) and unchanged expression of AQP9 in rats subjected to normobaric hypoxia. In choroid plexus homogenates an 83% upregulation of AQP1 (p<0.001) following hypoxia was shown. Acetazolamide treatment prevented the upregulation of AQP1. The data support a role for cerebral AQP4 in clearing vasogenic oedema. Upregulation of AQP1 found in choroid plexi could hypothetically be accompanied by increased CSF‐volume. The reversion to control AQP1 levels after acetazolamide administration is suggestive of a mechanism responsible for the beneficial effect of the drug on clinical cerebral symptoms in AMS. This work was supported by the Beckett Foundation