EICOSANOID REGULATION OF FETAL PLACENTAL CIRCULATION

胎盘血流的潜在药理调节作用 逆转先兆子痫等引起的血管收缩 妊娠期高血压疾病取决于对 二十烷类化合物的复杂相互作用及其调控 这种循环中的机制。花生四烯酸的代谢物 酸在调节器官血流方面很重要，而且 母体和胎儿胎盘循环中的血管活性 种类繁多。前列腺素，由 环氧合酶途径，由血管扩张剂和 血管收缩药。白三烯，由5- 脂氧合酶途径，主要是血管收缩因子。 肺、心、肠、肺等器官的微循环 肾虚异位证多数可引起全身低血压 物种。人们对这些因素的影响知之甚少 体内胎儿胎盘血管系统上的物质，或 它们调节肌张力或调节血流的机制 送到这个器官。这项建议的重点是胎儿胎盘 非麻醉近期患者对二十烷基类化合物的血管反应 羊胎。血流量的变化将用 放射性核素标记微球技术。目标将是 确定1)胎儿是否服用血管扩张剂 前列环素对胎盘血管收缩的调节作用 血管紧张素II或血栓素；2)胎儿给药 外源性白三烯会导致胎盘血管收缩； 阻断胎儿内源性白三烯将导致 胎盘血管扩张；4)正常绵羊胎盘产生 前列环素、血栓素A和5-脂氧合酶代谢产物 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.