Watanabe T, Matsuhashi K, Takayama S, Morita H
Nihon Yakurigaku Zasshi. 1984 Aug;84(2):229-41.
The drugs acting on the autonomic nervous system were administered intravenously to dams or intraperitoneally to the 20-day-old fetuses maintained by umbilical and placental circulation. The fetal heart rates were accelerated by the administration of isoproterenol, epinephrine, norepinephrine, tyramine and dopamine to fetuses, and they were decelecated by the injection of propranolol and methacholine to fetuses. However, the tachycardia caused by the fetal injection of isoproterenol and the bradycardia by methacholine were inhibited by the pretreatment of propranolol and atropine. The fetal bradycardia and hypoxia caused by the administration of epinephrine under the pretreatment of propranolol to fetuses were inhibited by the injection of alpha-adrenergic receptor blockers such as phentolamine and yohimbine. Furthermore, the tyramine treatment to fetuses produced significant acceleration of the fetal heart rate on day 19-20 of gestation, but not on day 18. These findings suggest that fetal cardiac beta-adrenergic, muscarine-cholinergic receptors and vascular postsynaptic alpha-adrenergic receptor may be sensitive enough to respond to sympathomimetic and sympatholytic drugs, and the fetal cardiac sympathetic innervation between the adrenergic nerve terminal and synapse effector cells may be developed on day 18-19 of gestation.
作用于自主神经系统的药物通过静脉注射给予母鼠，或通过腹腔注射给予由脐循环和胎盘循环维持的20日龄胎儿。给胎儿注射异丙肾上腺素、肾上腺素、去甲肾上腺素、酪胺和多巴胺可使胎儿心率加快，而给胎儿注射普萘洛尔和乙酰甲胆碱可使胎儿心率减慢。然而，预先用普萘洛尔和阿托品处理可抑制胎儿注射异丙肾上腺素引起的心动过速以及乙酰甲胆碱引起的心动过缓。在给胎儿预先用普萘洛尔处理的情况下，注射肾上腺素所引起的胎儿心动过缓和缺氧可被注射酚妥拉明和育亨宾等α-肾上腺素能受体阻滞剂所抑制。此外，对胎儿进行酪胺处理在妊娠第19 - 20天可使胎儿心率显著加快，但在第18天则不然。这些发现表明，胎儿心脏的β-肾上腺素能、毒蕈碱-胆碱能受体以及血管突触后α-肾上腺素能受体可能足够敏感，能够对拟交感神经药和抗交感神经药作出反应，并且胎儿心脏在肾上腺素能神经末梢和突触效应细胞之间的交感神经支配可能在妊娠第18 - 19天发育形成。
