From the Department of Obstetrics and Gynecology (A.S.C., J.S.M., E.P.H., S.T.D.), Department of Anesthesiology and Pain Medicine (S.L.B.), Women and Children's Health Research Institute (A.S.C., S.L.B., J.S.M., E.P.H., S.T.D.), Cardiovascular Research Centre (A.S.C., S.L.B., J.S.M., S.T.D.), University of Alberta, Edmonton, Alberta, Canada.
Hypertension. 2015 Jun;65(6):1324-30. doi: 10.1161/HYPERTENSIONAHA.115.05167. Epub 2015 Apr 27.
Advanced maternal age is becoming increasingly common in Western societies and is associated with increased maternal and fetal morbidity and mortality. We hypothesized that aging results in impaired vascular function in pregnancy because of increased vascular oxidative stress and resultant scavenging of nitric oxide in both uterine and systemic arteries, causing reduced uteroplacental perfusion and poor pregnancy outcomes. Using aged rats (9.5 months), we investigated the effect of a delayed first natural pregnancy on pregnancy outcomes and uterine and mesenteric artery function on gestational day 20. Delayed pregnancy in the rat reduced fertility by 46%, reduced litter size by 36%, caused fetal growth restriction, increased placental weight, and increased maternal systolic blood pressure (by 16 mm Hg). Uterine arteries from aged dams displayed reduced constriction to phenylephrine (young: 14.3±0.94 mN/mm versus aged: 11.4±0.5 mN/mm, P=0.02) and potassium chloride (124 mmol/L; young: 21.8±1.27 mN/mm versus aged: 14.2±1.7 mN/mm; P=0.01). Methacholine-induced vasodilation was similar in uterine arteries from young and aged dams. However, mesenteric arteries from aged dams had a greater nitric oxide and a reduced endothelial-derived hyperpolarization contribution to methacholine-mediated vasodilation compared with young dams. Both uterine and mesenteric arteries from aged dams had greater active myogenic responses, with area under the curve increased by 228% and 151%, in aged uterine and mesenteric arteries, respectively. These results demonstrate that vascular function is altered at an advanced maternal age and provides further insights into the risks of poor pregnancy outcomes observed in women who delay pregnancy.
高龄产妇在西方社会越来越常见，与产妇和胎儿发病率和死亡率增加有关。我们假设，由于血管氧化应激增加，以及子宫和全身动脉中一氧化氮的清除，导致胎盘灌注减少，妊娠结局不良，衰老会导致妊娠期间血管功能受损。我们使用老年大鼠（9.5 个月）研究了延迟第一次自然妊娠对妊娠结局以及妊娠第 20 天子宫和肠系膜动脉功能的影响。大鼠的延迟妊娠使受孕率降低 46%，胎仔数减少 36%，导致胎儿生长受限、胎盘重量增加和母体收缩压升高（16mmHg）。老年母鼠的子宫动脉对苯肾上腺素的收缩反应减弱（年轻组：14.3±0.94 mN/mm 对老年组：11.4±0.5 mN/mm，P=0.02）和氯化钾（124mmol/L；年轻组：21.8±1.27 mN/mm 对老年组：14.2±1.7 mN/mm；P=0.01）。年轻和老年母鼠子宫动脉对乙酰甲胆碱诱导的血管舒张反应相似。然而，与年轻母鼠相比，老年母鼠的肠系膜动脉对乙酰甲胆碱介导的血管舒张反应中一氧化氮增加，内皮源性超极化作用减少。与年轻母鼠相比，老年母鼠的子宫和肠系膜动脉的主动肌反应均增强，曲线下面积分别增加了 228%和 151%。这些结果表明，血管功能在高龄产妇中发生改变，并进一步深入了解了高龄产妇妊娠结局不良的风险。
