Gombos R B, Wolan V, McDonald K, Hemmings D G
Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada.
Am J Physiol Heart Circ Physiol. 2009 Apr;296(4):H937-45. doi: 10.1152/ajpheart.01027.2008. Epub 2009 Jan 30.
Human cytomegalovirus (CMV) is implicated in vascular complications through endothelial dysfunction. However, the effect of in vivo infections on vascular function in isolated arteries has not been examined. In pregnancy, systemic and uterine vascular adaptations accommodate increased blood volume through several mechanisms, including decreased sensitivity to vasoconstrictors and increased production of endothelial-dependent vasodilators. We hypothesized that an active in vivo CMV infection would reduce vasodilation of isolated arteries to the endothelial-dependent vasodilator methacholine and increase vasoconstriction to the alpha(1)-adrenergic receptor agonist phenylephrine and that these CMV-induced changes would be accentuated in late pregnancy. A mouse CMV infection model was used to study vascular responses in isolated mesenteric and uterine arteries from nonpregnant and late pregnant mice. In the mouse, CMV is not transmitted to the fetus. Accordingly, there was no evidence of active infection in any fetus examined, even though an active infection was found in salivary glands, uterine and mesenteric arteries, and placentas. Contrary to our hypothesis, increased endothelial-dependent vasodilation was found in mesenteric arteries from infected compared with uninfected nonpregnant and pregnant mice These data implicate active CMV infections in hypotensive disorders. Similarly, increased vasodilation was found in uterine arteries from infected vs. uninfected nonpregnant mice. However, this was completely reversed in infected compared with uninfected late pregnant mice in which vasodilation in uterine arteries was significantly reduced. Uterine arteries from infected pregnant mice also showed increased vasoconstriction to phenylephrine. Maternal infection led to decreased placental weights but had no effect on fetal weights in late pregnancy. These novel data demonstrate abnormal systemic and uterine vascular responses during an active CMV infection in both nonpregnant and late pregnant mice. Importantly, despite reduced placental weights, fetal weights were maintained, suggesting effective intrauterine compensation in the mouse model.
人巨细胞病毒（CMV）通过内皮功能障碍与血管并发症有关。然而，体内感染对分离动脉血管功能的影响尚未得到研究。在怀孕期间，全身和子宫血管适应通过多种机制来适应血容量增加，包括对血管收缩剂的敏感性降低和内皮依赖性血管舒张剂的产生增加。我们假设，体内活跃的CMV感染会降低分离动脉对内皮依赖性血管舒张剂乙酰甲胆碱的舒张作用，并增加对α（1）-肾上腺素能受体激动剂去氧肾上腺素的收缩作用，并且这些CMV诱导的变化在妊娠晚期会更加明显。使用小鼠CMV感染模型来研究未怀孕和妊娠晚期小鼠分离的肠系膜动脉和子宫动脉中的血管反应。在小鼠中，CMV不会传播给胎儿。因此，在所检查的任何胎儿中均未发现活跃感染的证据，尽管在唾液腺、子宫和肠系膜动脉以及胎盘中发现了活跃感染。与我们的假设相反，与未感染的未怀孕和怀孕小鼠相比，感染小鼠的肠系膜动脉中内皮依赖性血管舒张增加。这些数据表明活跃的CMV感染与低血压疾病有关。同样，与未感染的未怀孕小鼠相比，感染小鼠的子宫动脉中血管舒张增加。然而，与未感染的妊娠晚期小鼠相比，这种情况在感染小鼠中完全逆转，其中子宫动脉中的血管舒张明显减少。感染的妊娠小鼠的子宫动脉对去氧肾上腺素的收缩作用也增加。母体感染导致胎盘重量减轻，但对妊娠晚期的胎儿体重没有影响。这些新数据表明，在未怀孕和妊娠晚期小鼠的活跃CMV感染期间，全身和子宫血管反应异常。重要的是，尽管胎盘重量减轻，但胎儿体重得以维持，这表明在小鼠模型中存在有效的宫内补偿。
