Chronic binge alcohol exposure during pregnancy impairs rat maternal uterine vascular function.
Chronic binge alcohol exposure during pregnancy impairs rat maternal uterine vascular function.
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DOI：
10.1111/acer.12431
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发表时间：
2014-07
期刊：
影响因子：
--
通讯作者：
Ramadoss J
中科院分区：
文献类型：
--
作者：
Subramanian K;Naik VD;Sathishkumar K;Yallampalli C;Saade GR;Hankins GD;Ramadoss J
怀孕期间接触酒精会导致一系列结构和功能异常，称为胎儿酒精谱系障碍 (FASD)。酒精会导致子宫脉管系统精细的协调和妊娠适应调节失调。我们在此假设，慢性酗酒会损害母体子宫动脉对血管收缩剂和扩张剂的反应性，并且酒精引起的血管功能障碍依赖于内皮细胞。我们在怀孕大鼠模型系统中采用了每日一次的暴饮暴食酒精（4.5 g/kg 体重）暴露模式（妊娠日 (GD) 7-17），并利用线肌描记法研究了初级子宫动脉功能对血管收缩剂和血管扩张剂的反应。酒精（血液酒精浓度峰值，216 mg/dl）会导致子宫血管功能障碍，但母体和胎儿体重、胎儿头臀长和胎盘重量没有明显可见的生长缺陷。酒精不会改变子宫血管对α1肾上腺素能激动剂去氧肾上腺素或前列腺素血栓素的反应性。然而，酒精会特别损害内皮依赖性乙酰胆碱（Ach）介导的子宫动脉血管舒张，但外源性内皮非依赖性血管舒张剂（如硝普钠）则没有酒精作用。 Ach 显着降低血管松弛（P=0.003；↓pD2（产生半最大响应的负对数摩尔 Ach 浓度），-7.004±0.215 与-6.310±0.208；EMax（最大 Ach 响应），92% 与 75%）。我们的结论是，适量饮酒会损害孕妇的子宫血管功能。酒精会特别损害内皮依赖性激动剂诱导的子宫动脉血管舒张。综上所述，母体子宫腔室可能在 FASD 的发病机制中发挥重要作用。因此，需要考虑酒精在母亲和胎儿水平上的机制目标，以便制定有效的 FASD 治疗策略。
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 impairs maternal uterine artery reactivity to vasoconstrictors and dilators and that alcohol-induced vascular dysfunction is dependent on the endothelium. We utilized a once-daily binge alcohol (4.5 g/kg body weight) exposure paradigm (gestational day (GD) 7-17) in a pregnant rat model system and investigated primary uterine artery function in response to vasoconstrictors and vasodilators utilizing wire myography. Alcohol (peak blood alcohol concentration, 216 mg/dl) produced uterine vascular dysfunction in the absence of grossly observable growth deficits in maternal and fetal body weights, fetal crown-rump length and placental weight. Alcohol did not produce altered uterine vascular reactivity to α1 adrenergic agonist phenylephrine or the prostanoid thromboxane. However, alcohol specifically impaired endothelium-dependent 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%). We conclude that moderate alcohol exposure impairs uterine vascular function in pregnant mothers. Alcohol specifically impairs endothelium-dependent 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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影响因子：
3.6
作者：
Cooke, CLM;Davidge, ST
通讯作者：
Davidge, ST
DOI：
10.1111/j.1530-0277.2006.00116.x
发表时间：
2006-06-01
期刊：
ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH
影响因子：
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