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Hemodynamic effects of teratogenic agents on cardiovasculat function during early developmental stage of morphogenesis

致畸剂对形态发生早期发育阶段心血管功能的血流动力学影响

基本信息

批准号：
61570474
负责人：
NAKAZAWA Makoto
金额：
$ 1.34万
依托单位：
Tokyo Women's Mecical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1987
项目状态：
已结题

项目摘要

Hemodynamic alteration during early stage of development id known to influence cardiovascular morphogenesis. We have investigated the effect of cardioactive agents, whish has also known to be teratogenic in the chick, on the catdiovascular function in the stage 21 check embryo. It was found that isoproterenol and carreine brought about the hemodynamic alteration, which could be positively related to the abnormal morphogenesis of these agents. The eddect of acetylcholine, however, was not found to have a major role in its cardiovascular teratogenesis. We developed a new method to measure the blood pressure and flow parameter(which would estimate cardiac output) in the rat embrto, and obtained"normal" data at 11 to 15 days of gestation. It is reported that caffeine induces different type of cardiovascular anomalies between rat and chick embryos. The effects of caffeine in the rat embryo was different from those in chick embryo, suggesting that the different hemodynamic alteration has a significant role in their different morphogenesis. Bisdiamine is a cardivacular teratogene, which is considered to act by interfering with normal neural crest cell migration. It is reported that neural crest cell ablation affects vagel development. Thus we investigated the effect of bisdiamine, given to pregnant rats, on the hemodynamics of their embryo, and the effect of acetylcholine challenge. The hemodynamic parameters before the challenge were similar between the bisdiamine treated group and the control group. The response of heart rate to acetylcholine was less in the treated ewmbryo, suggesting that bidsiamine might have some direct effect on normal neural crest cell development in the rat model. We conclude that cardioactive agents may be classified into two groups according to the relationship between their hemodynamic effect and teratogenecity ; one brings about its teratogenecity through hemodynamic effect and another does it not by hemodynamic effect.

已知发育早期的血流动力学改变影响心血管形态发生。我们研究了心脏活性药物对21期鸡胚心血管功能的影响，这些药物也已知对鸡有致畸作用。结果发现异丙肾上腺素和卡琳引起的血流动力学改变可能与它们的异常形态发生有关。然而，乙酰胆碱的排泄在其心血管致畸作用中没有发现主要作用。我们发展了一种新的方法来测量血压和血流参数（这将估计心输出量）在大鼠胚胎，并获得了“正常”的数据在11至15天的妊娠。据报道，咖啡因可诱发大鼠和鸡胚不同类型的心血管畸形。咖啡因对大鼠胚胎和鸡胚胎的影响不同，提示不同的血流动力学改变在它们不同的形态发生中起重要作用。双二胺是一种心血管致畸剂，被认为是通过干扰正常的神经嵴细胞迁移而起作用。据报道，神经嵴细胞消融影响迷走神经发育。因此，我们研究了双二胺，给予妊娠大鼠，对他们的胚胎的血流动力学的影响，和乙酰胆碱的挑战的影响。双二胺处理组和对照组之间激发前的血流动力学参数相似。在处理的胚胎中，心率对乙酰胆碱的反应较小，表明bidsiamine可能对大鼠模型中正常神经嵴细胞的发育有一些直接影响。我们认为，根据其血流动力学效应与致畸性的关系，心脏活性药物可分为两类，一类是通过血流动力学效应引起致畸性，另一类不是通过血流动力学效应引起致畸性。