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Adrenomedullin reduces gender dependent loss of hypotensive cerebrovasodilation after newborn brain injury through activation of ATP dependent K channels
Author(s) -
Armstead William M,
Vavilala Monica
Publication year - 2007
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.21.6.a1387-b
Subject(s) - medicine , adrenomedullin , antagonist , glibenclamide , iberiotoxin , endocrinology , endogeny , anesthesia , potassium channel , receptor , diabetes mellitus
Cerebrovascular dysregulation during hypotension occurs after fluid percussion brain injury (FPI) in the newborn pig due to impaired K channel function. This study was designed to: determine the role of K channels in adrenomedullin (ADM) cerebrovasodilation, characterize the role of gender in the loss of hypotensive cerebrovasodilation after FPI, and determine the ability of exogenous ADM to modulate hypotensive dysregulation after FPI. Lateral FPI (2 atm) was induced in newborn male and female newborn pigs (1–5 days old) equipped with a closed cranial window, n=6 for each protocol. ADM induced pial artery dilation (PAD) was significantly greater in female than male piglets and blocked by the ATP K channel antagonist glibenclamide, but not by the Ca K channel antagonist iberiotoxin. CSF ADM was increased from 3.8 +/− 0.7 to 14.6 +/− 3.0 fmole/ml after FPI in female but was unchanged in male piglets. Hypotensive PAD was blunted to a significantly greater degree in male versus female piglets after FPI. Topical pretreatment with a subthreshold vascular concentration of ADM (10 −10 M) prior to FPI reduced the loss of hypotensive PAD in both genders, but protection was significantly greater in male versus female piglets. These data show that hypotensive PAD is impaired after FPI in a gender dependent manner. By unmasking a gender dependent endogenous protectant, these data suggest novel gender dependent approaches for clinical intervention in the treatment of perinatal traumatic brain injury.