Department of Physiology, University of Alberta, Edmonton, Alberta, Canada.
Am J Physiol Heart Circ Physiol. 2010 Oct;299(4):H1124-34. doi: 10.1152/ajpheart.01113.2009. Epub 2010 Jul 30.
Chronic cytomegalovirus (CMV) infections are implicated in vascular diseases. Recently, we showed that an active mouse CMV (mCMV) infection in nonpregnant mice increased endothelial-dependent vasodilation in isolated mesenteric and uterine arteries. In late pregnancy, while increased vasodilation was found in mesenteric arteries from infected mice, there was a dramatic decrease in uterine arteries. Understanding the mechanisms for these vascular changes during CMV infections is important for pregnancy outcomes and long-term consequences of this chronic infection. Increased nitric oxide (NO) is implicated in CMV-associated atherosclerosis, and CMV replication is dependent on prostaglandin H synthase (PGHS) activity. Alternatively, CMV infections decrease NO under inflammatory conditions. We therefore hypothesized that changes in the contribution by NO or PGHS-induced vasodilators would explain the increased or decreased endothelial-dependent vasodilation in arteries from nonpregnant and late pregnant mice, respectively. We found that the contribution by NO to methacholine-induced vasodilation was significantly increased in mesenteric, but not uterine, arteries isolated from nonpregnant and pregnant mCMV-infected mice. Prostaglandin inhibition did not affect endothelial-dependent vasodilation in any group. Vasodilation responses to sodium nitroprusside, an NO donor, were increased in mesenteric and uterine arteries isolated only from mCMV-infected nonpregnant mice. These results explain the increased vasodilation responses observed in mesenteric arteries from mCMV-infected mice; however, the decreased vasodilation in uterine arteries from pregnant mice could not be explained by these mechanisms. Thus CMV infection affects the contribution of NO differently in endothelial-dependent vasodilation in pregnant compared with nonpregnant mice and also in the mesenteric compared with the uterine vascular bed.
慢性巨细胞病毒 (CMV) 感染与血管疾病有关。最近，我们发现非妊娠小鼠的活跃性 CMV (mCMV) 感染会增加分离的肠系膜和子宫动脉的内皮依赖性血管舒张。在妊娠晚期，虽然感染小鼠的肠系膜动脉中发现血管舒张增加，但子宫动脉的血管舒张显著减少。了解 CMV 感染期间这些血管变化的机制对于妊娠结局和这种慢性感染的长期后果非常重要。一氧化氮 (NO) 的增加与 CMV 相关的动脉粥样硬化有关，CMV 的复制依赖于前列腺素 H 合酶 (PGHS) 活性。相反，CMV 感染会在炎症条件下减少 NO。因此，我们假设 NO 或 PGHS 诱导的血管扩张剂的变化将分别解释非妊娠和妊娠晚期小鼠动脉中内皮依赖性血管舒张的增加或减少。我们发现，NO 对麦角新碱诱导的血管舒张的贡献在非妊娠和妊娠 mCMV 感染小鼠的肠系膜动脉中显著增加，但在子宫动脉中没有增加。前列腺素抑制在任何组中均不影响内皮依赖性血管舒张。仅来自 mCMV 感染的非妊娠小鼠的肠系膜和子宫动脉对硝普钠（一种 NO 供体）的血管舒张反应增加。这些结果解释了在 mCMV 感染小鼠的肠系膜动脉中观察到的血管舒张反应增加；然而，不能用这些机制来解释妊娠小鼠子宫动脉中血管舒张的减少。因此，CMV 感染以不同的方式影响非妊娠和妊娠小鼠以及肠系膜和子宫血管床中内皮依赖性血管舒张中 NO 的贡献。
