Experimental studies in animal models supporting protective effects on the fetus of melatonin in adverse pregnancy have prompted clinical trials in human pregnancy complicated by fetal growth restriction. However, the effects of melatonin on the fetal defense to acute hypoxia, such as that which may occur during labor, remain unknown. This translational study tested the hypothesis, in vivo, that melatonin modulates the fetal cardiometabolic defense responses to acute hypoxia in chronically instrumented late gestation fetal sheep via alterations in fetal nitric oxide (NO) bioavailability. Under anesthesia, 6 fetal sheep at 0.85 gestation were instrumented with vascular catheters and a Transonic flow probe around a femoral artery. Five days later, fetuses were exposed to acute hypoxia with or without melatonin treatment. Fetal blood was taken to determine blood gas and metabolic status and plasma catecholamine concentrations. Hypoxia during melatonin treatment was repeated during in vivo NO blockade with the NO clamp. This technique permits blockade of de novo synthesis of NO while compensating for the tonic production of the gas, thereby maintaining basal cardiovascular function. Melatonin suppressed the redistribution of blood flow away from peripheral circulations and the glycemic and plasma catecholamine responses to acute hypoxia. These are important components of the fetal brain sparing response to acute hypoxia. The effects of melatonin involved NO-dependent mechanisms as the responses were reverted by fetal treatment with the NO clamp. Melatonin modulates the in vivo fetal cardiometabolic responses to acute hypoxia by increasing NO bioavailability.

中文翻译：

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褪黑激素调节胎儿对急性缺氧的心血管防御反应。

支持在不良妊娠中褪黑激素对胎儿的保护作用的动物模型的实验研究促使临床试验在人类妊娠合并胎儿生长受限的情况下进行。然而，褪黑激素对胎儿抵抗急性缺氧的影响，例如在分娩期间可能发生的影响，仍然未知。这项转化研究在体内验证了这一假设，即褪黑激素通过改变胎儿一氧化氮 (NO) 的生物利用度来调节长期使用仪器仪表的晚期妊娠胎羊对急性缺氧的胎儿心脏代谢防御反应。在麻醉下，6 只 0.85 妊娠的胎羊在股动脉周围安装了血管导管和跨音速流量探头。五天后，胎儿在有或没有褪黑激素治疗的情况下暴露于急性缺氧环境。采集胎儿血液以确定血气和代谢状态以及血浆儿茶酚胺浓度。褪黑激素治疗期间的缺氧在用 NO 钳进行体内 NO 阻断期间重复。该技术允许阻断 NO 从头合成，同时补偿气体的补品产生，从而维持基础心血管功能。褪黑激素抑制血流从外周循环的重新分配以及血糖和血浆儿茶酚胺对急性缺氧的反应。这些是胎儿大脑对急性缺氧反应的重要组成部分。褪黑激素的作用涉及 NO 依赖性机制，因为反应被胎儿用 NO 钳治疗逆转。褪黑激素通过增加 NO 生物利用度来调节体内胎儿对急性缺氧的心脏代谢反应。