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Chronic Binge Alcohol Exposure During Pregnancy Impairs Rat Maternal Uterine Vascular Function
Author(s) -
Subramanian Kaviarasan,
Naik Vishal D.,
Sathishkumar Kunju,
Yallampalli Chandrashekar,
Saade George R.,
Hankins Gary D.,
Ramadoss Jayanth
Publication year - 2014
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.12431
Subject(s) - vasodilation , medicine , uterine artery , preeclampsia , endocrinology , alcohol , phenylephrine , pregnancy , gestation , chemistry , biology , blood pressure , biochemistry , genetics
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 α 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; ↓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.