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In Utero Exposure to Alcohol Alters Reactivity of Cerebral Arterioles
Author(s) -
Cananzi Sergio Giuseppe,
Mayhan William Gerard
Publication year - 2016
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.30.1_supplement.953.14
Subject(s) - in utero , hypercapnia , endocrinology , medicine , cerebral blood flow , enos , cerebral cortex , middle cerebral artery , nitric oxide , nitric oxide synthase , chemistry , anesthesia , fetus , pregnancy , ischemia , biology , acidosis , genetics
Background Fetal alcohol spectrum disorders (FASD) have long been linked with developmental abnormalities that often result in brain damage and mental disabilities. It is conceivable that these abnormalities may be related alterations in the regulation of cerebral blood flow (CBF) by in utero exposure to alcohol. Our goal was to examine whether in utero alcohol impaired reactivity of cerebral arterioles during development. Methods Sprague‐Dawley dams were fed a liquid diet with or without alcohol (3% and 6.4%) for the duration of pregnancy (about 21 days). The pups were weaned at three weeks of age. At four weeks of age, we measured CBF (Laser Doppler) in pups in response to hypercapnia. In addition, we made a craniotomy over the parietal cortex and measured responses of cerebral arterioles to agonists that activate endothelial Nitric Oxide Synthase (ADP), neuronal Nitric Oxide Synthase (NMDA), and an agonist that dilates independent of NOS (nitroglycerin). We also used an inhibitor of NOS (L‐NMMA) and tested responses to agonists of eNOS and nNOS. We also measured the expression of NOX‐2 in the brain cortex. Results In utero exposure to alcohol (3 and 6.4%) attenuated rCBF responses to hypercapnia. Responses to agonists that activate eNOS were reduced in cerebral arterioles of alcohol pups. Nitroglycerin produced similar responses in all groups. Protein expression of NOX‐2 from cortex tissue was increased in both 3% and 6.4% alcohol groups. Conclusions Our findings suggest that in utero alcohol exposure negatively affects the cerebral arterioles and that NOX‐2 may play an important role in the observed impairments. Vascular dysfunction and upregulated expression of NOX‐2 may increase infarct damage from ischemic stroke during FASD. Support or Funding Information LSU Health Sciences Center‐Shreveport and the Center for Cardiovascular Diseases and Sciences.