Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1/12, 119234, Moscow, Russia; Institute for Biomedical Problems, Russian Academy of Sciences, Khoroshevskoe Shosse 76A, 123007, Moscow, Russia; Department of Physiology, Russian National Research Medical University, Ostrovitianova Str. 1, 117997, Moscow, Russia.
Institute for Biomedical Problems, Russian Academy of Sciences, Khoroshevskoe Shosse 76A, 123007, Moscow, Russia.
Nitric Oxide. 2018 Apr 1;74:10-18. doi: 10.1016/j.niox.2018.01.001. Epub 2018 Jan 5.
Our recent study showed that NO-mediated anticontractile effect of endothelium is absent in coronary arteries of adult rats, which suffered from antenatal/early postnatal hypothyroidism. This study tested the hypothesis that exercise training would improve such detrimental consequences of early thyroid deficiency.
Wistar dams received propylthiouracil (PTU, 7 ppm) in drinking water during gestation and two weeks postpartum; control dams received tap water. Six-week-old male offspring of control (CON) and PTU dams was divided into sedentary (CON-Sed, n = 12; PTU-Sed, n = 10) and trained (CON-Tr, n = 12; PTU-Tr, n = 10) groups; the latter had 24-h access to running wheels. Eight weeks later coronary arteries were studied by wire myography. Anticontractile effect of NO was assessed by the effects of NOS inhibitor L-NNA on the basal tone and contractile response to U46619. Oxidative phosphorylation complexes and eNOS were estimated by Western blotting.
T/T and TSH levels (ELISA) were normalized in the progeny of PTU-treated dams at the age of 6 weeks and were not affected by training. Total running distance did not differ between CON-Tr and PTU-Tr. The contents of oxidative phosphorylation complexes were increased post-training in triceps brachii muscle from CON-Tr and PTU-Tr and in heart from PTU-Tr. Coronary arteries of PTU-Sed compared to CON-Sed demonstrated higher basal tone and contractile response to U46619, which were not further increased by L-NNA. The effects of L-NNA on the basal tone and contractile response to U46619 did not differ in CON-Tr and PTU-Tr groups, but were elevated in PTU-Tr compared to PTU-Sed group. PTU-Tr rats in comparison to PTU-Sed group had higher eNOS content in heart. Responses of coronary arteries to DEA/NO did not differ among all experimental groups.
Long-lasting coronary endothelial dysfunction resulted from transient thyroid deficiency during the antenatal/early postnatal period can be corrected by voluntary exercise training.
我们最近的研究表明，在经历过产前/产后早期甲状腺功能减退的成年大鼠的冠状动脉中，内皮介导的 NO 抗收缩作用缺失。本研究检验了这样一个假设，即运动训练可以改善早期甲状腺功能不足的这种有害后果。
Wistar 孕鼠在孕期和产后两周内通过饮用水摄入丙硫氧嘧啶（PTU，7ppm）；对照组孕鼠则摄入自来水。对照组（CON）和 PTU 组雄性仔鼠 6 周龄时被分为安静组（CON-Sed，n=12；PTU-Sed，n=10）和训练组（CON-Tr，n=12；PTU-Tr，n=10）；后者 24 小时可接触跑轮。8 周后，通过线描法研究冠状动脉。通过 NOS 抑制剂 L-NNA 对基础张力和 U46619 收缩反应的影响，评估 NO 的抗收缩作用。通过 Western 印迹法估计氧化磷酸化复合物和 eNOS。
6 周龄时，PTU 处理母鼠后代的 T/T 和 TSH 水平（ELISA）恢复正常，且不受训练影响。CON-Tr 和 PTU-Tr 的总跑步距离没有差异。CON-Tr 和 PTU-Tr 的肱三头肌以及 PTU-Tr 的心脏中氧化磷酸化复合物的含量在训练后增加。与 CON-Sed 相比，PTU-Sed 的冠状动脉基础张力和对 U46619 的收缩反应更高，而 L-NNA 则不能进一步增加。L-NNA 对基础张力和 U46619 收缩反应的影响在 CON-Tr 和 PTU-Tr 组之间没有差异，但在 PTU-Tr 组中高于 PTU-Sed 组。与 PTU-Sed 组相比，PTU-Tr 大鼠的心脏 eNOS 含量更高。各组冠状动脉对 DEA/NO 的反应无差异。
产前/产后早期短暂性甲状腺功能减退引起的长期冠状动脉内皮功能障碍可通过自愿运动训练纠正。
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