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In Utero Exposure to Alcohol Impairs Reactivity of Cerebral Arterioles and Increases Susceptibility of the Brain to Damage Following Ischemia/Reperfusion in Adulthood
Author(s) -
Cananzi Sergio G.,
Mayhan William G.
Publication year - 2019
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13979
Subject(s) - in utero , medicine , offspring , endocrinology , ischemia , apocynin , brain damage , anesthesia , middle cerebral artery , nitric oxide synthase , nitric oxide , oxidative stress , pregnancy , fetus , biology , genetics , nadph oxidase
Background Maternal consumption of alcohol produces abnormalities in the developing fetus and can contribute to an increased incidence of many cardiovascular‐related diseases. The first goal of this study was to determine whether in utero exposure to alcohol influences reactivity of cerebral arterioles in adult (12 to 15 weeks old) rats. The second goal of this study was to examine whether in utero exposure to alcohol increased the susceptibility of the brain to damage following an ischemic event in adult rats. Methods We fed Sprague Dawley dams a liquid diet with or without alcohol (3% ethanol) for the duration of their pregnancy (21 to 23 days). In the first series of studies, we examined reactivity of cerebral arterioles to endothelial nitric oxide synthase (eNOS)‐ (adenosine diphosphate [ADP]) and neuronal nitric oxide synthase (nNOS)‐dependent N‐methyl‐D‐aspartate (NMDA, and NOS‐independent agonists in adult rats before and during application of l ‐ NMMA . In another series of studies, we examined infarct volume following middle cerebral artery occlusion in adult offspring exposed to alcohol in utero. In both series of studies, we also determined the role for an increase in oxidative stress by feeding dams apocynin for the duration of their pregnancy. Results We found that in utero exposure to alcohol reduced responses of cerebral arterioles to ADP and NMDA , but not to nitroglycerin in adult rats. In addition, treatment of the dams with apocynin prevented this impairment in cerebral vascular function. We also found that in utero exposure to alcohol worsened brain damage following ischemia/reperfusion in adult rats and that treatment of dams with apocynin prevented this increase in brain damage following ischemia/reperfusion. Conclusions We suggest that our findings may have important implications for the pathogenesis of brain abnormalities associated with fetal alcohol exposure.