成年甲状腺功能减退症大鼠的冠状动脉内皮介导的抗收缩作用消失。
NO-mediated anticontractile effect of the endothelium is abolished in coronary arteries of adult rats with antenatal/early postnatal hypothyroidism.
机构信息
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.
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.
出版信息
Nitric Oxide. 2017 Feb 28;63:21-28. doi: 10.1016/j.niox.2016.12.007. Epub 2016 Dec 23.
INTRODUCTION
Thyroid hormones are essential for proper development of many systems and organs, including circulatory system. Thyroid deficiency during pregnancy may affect the cardiovascular function in children early on and later in adulthood. However, long-term effects of early thyroid deficiency are poorly understood. We hypothesized that antenatal/early postnatal hypothyroidism will influence anticontractile effect of NO in coronary arteries of adult rats.
DESIGN AND METHODS
To model antenatal/early postnatal hypothyroidism dams were treated with 6-propyl-2-thiouracil (PTU) in drinking water (0.0007%, w/v) from the first day of pregnancy till 2 weeks after delivery. Control females were supplied with pure water. Their male offspring was grown up till the age of 10-12 weeks. Systolic blood pressure was measured using tail cuff method. Septal coronary arteries were isolated and studied in wire myograph. Blood serum thyroid hormones concentrations (ELISA) and NO metabolites level (Griess method) were evaluated.
RESULTS
At the age of 10-12 weeks thyroid hormones, TSH concentrations, NO metabolites and systolic blood pressure level didn't differ between groups. Arterial responses to acetylcholine and exogenous NO-donor DEA/NO were similar in control and PTU groups. Along with that, in control rats endothelium denudation strongly potentiated basal tone of arteries and their contractile responses to thromboxane A2 receptor agonist U46619. The effects of endothelium denudation were absent in PTU rats indicating that anticontractile effect of endothelium is abolished in their arteries. Further, NO-synthase inhibitor L-NNA (100 μM) caused significant elevation of basal tone and increased U46619-induced contraction of endothelium-intact arteries only in control rats, while had no effect in PTU group.
CONCLUSIONS
Our data demonstrate that NO-mediated anticontractile effect of endothelium is eliminated in coronary arteries of adult rats, which suffered from antenatal/early postnatal hypothyroidism. Therefore, maternal thyroid hormones deficiency may have detrimental consequences in adult offspring including coronary circulation pathologies, despite normal blood levels of thyroid hormones.
简介
甲状腺激素对包括循环系统在内的许多系统和器官的正常发育至关重要。妊娠期间甲状腺功能减退可能会影响儿童早期和成年后的心血管功能。然而，早期甲状腺功能减退的长期影响还知之甚少。我们假设产前/产后早期甲状腺功能减退会影响成年大鼠冠状动脉中 NO 的抗收缩作用。
设计和方法
为了建立产前/产后早期甲状腺功能减退模型，从妊娠第一天起，用丙基硫氧嘧啶（PTU）处理饮用水（0.0007%，w/v），直至分娩后 2 周。对照组雌性动物提供纯净水。他们的雄性后代长到 10-12 周大。用尾套法测量收缩压。分离并在电生理记录仪中研究室间隔冠状动脉。用 ELISA 法测定血清甲状腺激素浓度（TSH）和一氧化氮代谢物水平（Griess 法）。
结果
在 10-12 周龄时，两组间甲状腺激素、TSH 浓度、NO 代谢物和收缩压水平无差异。乙酰胆碱和外源性 NO 供体 DEA/NO 对动脉的作用在对照组和 PTU 组相似。此外，在对照组大鼠中，内皮剥脱强烈增强了动脉的基础张力及其对血栓烷 A2 受体激动剂 U46619 的收缩反应。PTU 大鼠的内皮剥脱作用不存在，表明其动脉的内皮抗收缩作用被消除。此外，NO 合酶抑制剂 L-NNA（100 μM）仅在对照组大鼠中引起基础张力显著升高，并增加内皮完整动脉中 U46619 诱导的收缩，而在 PTU 组中没有作用。
结论
我们的数据表明，患有产前/产后早期甲状腺功能减退的成年大鼠冠状动脉中，NO 介导的内皮抗收缩作用被消除。因此，尽管甲状腺激素的血液水平正常，但母体甲状腺激素缺乏可能会对成年后代产生有害影响，包括冠状动脉循环病理学。
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