title: Chronic binge alcohol exposure during pregnancy impairs rat maternal uterine vascular function.
abstract: 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 α1 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; ↓pD2 [negative log molar ACh concentration producing the half maximum response], -7.004 ± 0.215 vs. -6.310 ± 0.208; EMax [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.
authors: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas.
authors: Kaviarasan
authors: K
authors: Subramanian
authors: Vishal D
authors: VD
authors: Naik
authors: Kunju
authors: K
authors: Sathishkumar
authors: Chandrashekar
authors: C
authors: Yallampalli
authors: George R
authors: GR
authors: Saade
authors: Gary D
authors: GD
authors: Hankins
authors: Jayanth
authors: J
authors: Ramadoss
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D063425:Binge Drinking / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage* / Q000494:pharmacology*; D005260:Female; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D021041:Placental Circulation / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D013931:Thromboxanes / Q000494:pharmacology; D055988:Uterine Artery / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D013931:Thromboxanes; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D000431:Ethanol; D000109:Acetylcholine
keywords: Alcohol; Endothelium; Fetal Alcohol Spectrum Disorders; Maternal; Uterine; Vascular