Pregnancy-induced alterations of vascular function in mouse mesenteric and uterine arteries
Pregnancy-induced alterations of vascular function in mouse mesenteric and uterine arteries
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DOI：
10.1095/biolreprod.102.009886
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发表时间：
2003-03-01
影响因子：
3.6
通讯作者：
Davidge, ST
中科院分区：
文献类型：
--
作者：
Cooke, CLM;Davidge, ST
正常妊娠涉及母体血管功能的巨大变化，而异常的血管适应可能导致妊娠相关疾病，如先兆子痫。最近出现了许多遗传小鼠模型来研究妊娠的血管病理。然而，正常小鼠对妊娠的血管适应性尚不完全清楚。因此，我们研究了正常小鼠妊娠期间血管反应性的变化。我们假设，与非妊娠小鼠相比，妊娠小鼠通过增强一氧化氮合酶（NOS）、前列腺素H合酶（PGHS）和其他内皮源性超极化途径，增强了内皮依赖性血管舒张。将晚期妊娠（第17-18天）C57 BL/6 J小鼠（n = 10）与非妊娠小鼠（n = 7）进行比较。将子宫和肠系膜动脉固定在钢丝肌电描记系统上，并评估内皮依赖性（乙酰甲胆碱）和非依赖性（硝普钠; SNP）舒张反应。在妊娠子宫和肠系膜动脉中，内皮依赖性舒张增强，在加入PGHS或NOS通路抑制剂后，内皮依赖性舒张减弱。在非妊娠小鼠中，这些途径在调节子宫动脉舒张中没有作用，而肠系膜动脉的血管舒张仅通过NOS抑制而减少。子宫和肠系膜血管均具有正常的线粒体氧化物和非胰高血糖素介导的舒张，但这种舒张在妊娠期间没有增强。非内皮依赖性舒张也增强妊娠子宫动脉，但不是肠系膜动脉。我们的数据表明，子宫动脉和肠系膜动脉从怀孕小鼠有增强的血管舒张。了解正常小鼠妊娠的血管适应性对于解释遗传小鼠模型中可能发生的变化至关重要。
Normal pregnancy involves dramatic changes to maternal vascular function, while abnormal vascular adaptations may contribute to pregnancy-associated diseases such as preeclampsia. Many genetic mouse models have recently emerged to study vascular pathologies of pregnancy. However, vascular adaptations to pregnancy in normal mice are not fully understood. Thus, we studied changes in vascular reactivity during normal mouse pregnancy. We hypothesized that pregnant mice will have enhanced endothelial-dependent vasodilation compared with nonpregnant mice, via an enhancement of the nitric oxide synthase (NOS) prostaglandin H synthase (PGHS), and other endothelial -derived hyperpolarizing pathways. Late pregnant (Day 17-18) C57BL/6J mice (n = 10) were compared with nonpregnant mice (n = 7). Uterine and mesenteric arteries were mounted on a wire myograph system and assessed for endothelium-dependent (methacholine) and -independent (sodium nitroprusside; SNP) relaxation responses. Endothelial-dependent relaxation was enhanced in pregnant uterine and mesenteric arteries, which was blunted after the addition of inhibitors of the PGHS or NOS pathways. In nonpregnant mice, these pathways had no effect in modulating relaxation in uterine arteries, whereas vasodilation in mesenteric arteries was reduced only by NOS inhibition. Both uterine and mesenteric vessels had normitric oxide- and nonprostaglandin-mediated relaxation, but this relaxation was not enhanced during pregnancy. Endothelial-independent relaxation was also enhanced in pregnant uterine but not mesenteric arteries. Our data indicate that uterine and mesenteric arteries from pregnant mice have enhanced vasodilation. Understanding vascular adaptations to normal mouse pregnancy is crucial for interpreting changes that may occur in genetic mouse models.