EICOSANOID REGULATION OF FETAL PLACENTAL CIRCULATION

胎盘血流量的潜在药理学调节

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.