Journal
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
Volume 38, Issue 7, Pages 1832-1838Publisher
WILEY-BLACKWELL
DOI: 10.1111/acer.12431
Keywords
Fetal Alcohol Spectrum Disorders; Alcohol; Maternal; Uterine; Endothelium; Vascular
Categories
Funding
- NIAAA NIH HHS [K99 AA019446, R00 AA019446, AA19446] Funding Source: Medline
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Background: Alcohol exposure during pregnancy results in an array of structural and functional abnormalities called fetal alcohol spectrum disorders (FASD). Alcohol dysregulates the exquisite coordination and regulation of gestational adaptations at the level of the uterine vasculature. We herein hypothesized that chronic binge-like alcohol results in uterine vascular dysfunction and impairs maternal uterine artery reactivity to vasoconstrictors and dilators. Methods: We utilized a once-daily binge alcohol (4.5 g/kg body weight) exposure paradigm (gestational day 7 to 17) in a pregnant rat model system and investigated primary uterine artery function in response to vasoconstrictors and vasodilators utilizing wire myography. Results: Alcohol (peak blood alcohol concentration, 216 mg/dl) produced uterine vascular dysfunction. Alcohol did not produce altered uterine vascular reactivity to alpha 1 adrenergic agonist phenylephrine or the prostanoid thromboxane. However, alcohol specifically impaired acetylcholine (ACh)-mediated uterine artery vasodilation but exogenous endothelium-independent vasodilators like sodium nitroprusside exhibited no alcohol effect; ACh significantly decreased vessel relaxation (p = 0.003; down arrow pD(2) [negative log molar ACh concentration producing the half maximum response], -7.004 +/- 0.215 vs. -6.310 +/- 0.208; E-Max [maximal ACh response], 92% vs. 75%). Conclusions: We conclude that moderate alcohol exposure impairs uterine vascular function in pregnant mothers. Alcohol specifically impairs agonist-induced uterine artery vasodilation. In summary, the maternal uterine compartment may play a significant role in the pathogenesis of FASD. Thus, the mechanistic targets of alcohol at the level of both the mother and the fetus need to be considered in order to develop effective therapeutic treatment strategies for FASD.
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