Flow-mediated vasodilation is impaired in adult rat offspring exposed to prenatal hypoxia
Flow-mediated vasodilation is impaired in adult rat offspring exposed to prenatal hypoxia
复制标题
DOI：
10.1152/japplphysiol.01174.2010
复制
发表时间：
2011-04-01
影响因子：
3.3
通讯作者：
Davidge, S. T.
中科院分区：
文献类型：
--
作者：
Morton, J. S.;Rueda-Clausen, C. F.;Davidge, S. T.
现在已经证明低出生体重与晚年死亡率增加之间存在关联。胎儿发育的变化可能会影响心血管系统，并导致以后患心血管疾病的风险增加。此外，衰老是血管内皮依赖性功能障碍的危险因素。然而，宫内生长受限（IUGR）对血管功能障碍的正常衰老机制的影响尚不清楚。我们假设 IUGR 会引起血管功能的变化，从而以年龄或性别依赖性方式影响晚年血流诱导的血管舒张机制。为了创建 IUGR 模型，怀孕的 Sprague-Dawley 大鼠在怀孕第 15 天至 21 天期间被置于低氧（11.5% O-2）或对照（室内空气，21% O-2）环境中。雄性和雌性后代均在 4 个月或 12 个月大时进行了研究。在压力肌动描记器中使用血流诱导的血管舒张（一种血管舒张的生理刺激）来评估肠系膜小动脉的血管功能。血流诱导的血管舒张在年轻时不受影响，但与老龄对照组相比，在老年 IUGR 中显着降低（P < 0.05）。潜在的血管舒张机制发生了改变，使得一氧化氮介导的血管舒张作用在年轻成年和老年IUGR男性和女性以及衰老对照女性中被消除（P < 0.05）。所有组均维持内皮源性超极化因子介导的血管舒张（P < 0.01）。 IUGR 后代早期发生的血管舒张机制的变化可能会使他们在老年时容易患上心血管疾病。
There is now a demonstrated association between low birth weight and increased mortality later in life. Changes in fetal development may program the cardiovascular system and lead to an increased risk of cardiovascular diseases later in life. In addition, aging is a risk factor for vascular endothelial-dependent dysfunction. However, the impact of being born intrauterine growth restricted (IUGR) on the normal aging mechanisms of vascular dysfunction is not clear. We hypothesized that IUGR would cause changes in vascular function that would affect the mechanisms of flow-induced vasodilation later in life in an age-or sex-dependent manner. To create an IUGR model, pregnant Sprague-Dawley rats were placed in a hypoxic (11.5% O-2) or control (room air, 21% O-2) environment from days 15 to 21 of pregnancy. Both male and female offspring were investigated at 4 or 12 mo of age. Vascular function was assessed in small mesenteric arteries using flow-induced vasodilation, a physiological stimuli of vasodilation, in a pressure myograph. Flow-induced vasodilation was unaffected at a young age, but was significantly reduced in aging IUGR compared with aging controls (P < 0.05). Underlying vasodilator mechanisms were altered such that nitric oxide-mediated vasodilation was abolished in both young adult and aging IUGR males and females and in aging control females (P < 0.05). Endothelium-derived hyperpolarizing factor-mediated vasodilation was maintained in all groups (P < 0.01). A change in the mechanisms of vasodilation occurring at an earlier age in IUGR offspring may predispose them to develop cardiovascular diseases as an aging adult.