EICOSANOID REGULATION OF FETAL PLACENTAL CIRCULATION

胎盘血流的潜在药理学调节， 逆转先兆子痫和其他引起的血管收缩 妊娠期高血压疾病依赖于了解 类花生酸的复杂相互作用及其控制 在这个循环中。 花生四烯酸代谢 酸在器官血流的调节中很重要， 在母体和胎儿的胎盘循环中， 各种各样的物种。 生产的红葡萄酒 环氧合酶途径，包括血管扩张剂和 血管收缩剂 白细胞三烯，由5- 脂氧合酶途径，主要是血管收缩剂， 微循环的各种器官，如肺，心脏，肠道和 肾，但矛盾的是，在大多数情况下， 物种 对这些影响的了解相对较少 体内胎儿胎盘血管系统上的物质，或 它们调节张力或调节血流的机制 这个器官。 这项建议的重点是胎儿胎盘 在未麻醉的近期内血管对类二十烷酸的反应 羊胎儿 血液流量的变化将用 放射性核素标记微球技术。 目标将是 确定是否1）胎儿给予血管扩张剂 前列环素可以调节胎盘血管收缩， 血管紧张素II或血栓素; 2）胎儿施用 外源性白三烯会导致胎盘血管收缩; 3） 胎儿内源性白三烯的阻断将导致 胎盘血管舒张; 4）正常绵羊胎盘产生 前列环素、血栓素和5-脂氧合酶代谢物 花生四烯酸

Potential pharmacologic regulation of placental blood flow to reverse the vasconstriction caused by preeclampsia and other hypertensive disorders of pregnancy is dependent on understanding the complex interactions of eicosanoids and their control mechanisms within this circulation. Metabolites of arachidonic acid are important in the regulation of organ blood flow, and are vasoactive in both the maternal and fetal placental circulations of various species. The prostaglandins, produced by the cyclooxygenase pathway, consist of both vasodilators and vasoconstrictors. The leukotrienes, produced by the 5- lipoxygenase pathway, are primarily vasoconstrictors in the microcirculation of various organs such as lung, heart, gut and kidney but paradoxicallyu produce systemic hypotension in most species. Relatively little is known about the effects of these substances on the in vivo fetal placental vasculature, or the mechanisms by which they modulate tone or regulate blood flow to this organ. This proposal focuses on the fetal placental vascular responses to eicosanoids in the unanesthetized near term ovine fetus. Changes in blood blow will be measured with the radionuclide labeled microsphere technique. Objectives will be to determine if 1) fetal administration of the vasodilator prostacyclin can modulate placental vasoconstriction produced by angiotensin II or thromboxane; 2) fetal administration of exogenous leukotrienes will result in placental vasoconstriction; 3) blockade of endogenous leukotrienes in the fetus will result in placental vasodilation; 4) the normal ovine placenta produces prostacyclin, thromboxane and the 5-lipoxygenase metabolites of arachidonic acid.