Reimsnider Sharon, Wood Charles E
Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, Fla. 32610-0274, USA.
Neuroendocrinology. 2006;83(1):4-11. doi: 10.1159/000093177. Epub 2006 May 8.
BACKGROUND/AIMS: We have previously demonstrated that prostaglandin generation within the fetal brain augments or partially mediates fetal reflex responsiveness to hypotension. The present study was performed to test the relative roles of prostaglandin endoperoxide synthases-1 and -2 (PGHS-1 and 2, or COX-1 and 2) as potential mediators of this interaction.
Chronically catheterized and instrumented fetal sheep were subjected to transient brachiocephalic occlusion (BCO) after intracerebroventricular injection of resveratrol (PGHS-1 or COX-1 inhibitor), nimesulide (PGHS-2 or COX-2 inhibitor), or vehicle.
BCO decreased arterial pressure perfusing the fetal brain and stimulated increases in systemic blood pressure and heart rate as well as in circulating concentrations of ACTH. Inhibition of PGHS-1 and PGHS-2 had differential effects on fetal ACTH secretion. Pre-BCO concentrations of plasma ACTH increased in response to nimesulide, while the fetal ACTH response to BCO was delayed by resveratrol. Prior to the BCO, nimesulide also increased fetal blood pressure and decreased fetal heart rate. The injections of resveratrol and nimesulide did not alter placental biosynthesis of prostaglandins and therefore acted within the fetal brain.
We conclude that prostaglandin generated in the fetal brain by the action of PGHS-1 augments fetal ACTH reflex responses to BCO but that, in contrast, the action of PGHS-2 is inhibitory to ACTH secretion.
背景/目的：我们之前已经证明，胎儿脑内前列腺素的生成增强或部分介导了胎儿对低血压的反射反应。本研究旨在测试前列腺素内过氧化物合酶-1和-2（PGHS-1和2，或COX-1和2）作为这种相互作用潜在介质的相对作用。
在慢性插管并安装仪器的胎羊脑室内注射白藜芦醇（PGHS-1或COX-1抑制剂）、尼美舒利（PGHS-2或COX-2抑制剂）或赋形剂后，对其进行短暂的头臂动脉闭塞（BCO）。
BCO降低了灌注胎儿脑的动脉压，并刺激全身血压、心率以及促肾上腺皮质激素（ACTH）循环浓度升高。抑制PGHS-1和PGHS-2对胎儿ACTH分泌有不同影响。尼美舒利使BCO前血浆ACTH浓度升高，而白藜芦醇使胎儿对BCO的ACTH反应延迟。在BCO之前，尼美舒利还使胎儿血压升高并使胎儿心率降低。白藜芦醇和尼美舒利的注射并未改变胎盘前列腺素的生物合成，因此其作用于胎儿脑内。
我们得出结论，PGHS-1作用于胎儿脑内产生的前列腺素增强了胎儿对BCO的ACTH反射反应，但相反，PGHS-2的作用对ACTH分泌具有抑制作用。
