Foley J E, Gross D M, Nelson P K, Fisher J W
J Pharmacol Exp Ther. 1978 Nov;207(2):402-9.
The ability of arachidonic acid (AA), the bisenoic prostaglandin precursor to stimulate erythropoiesis and erythropoietin (Ep) production in exhypoxic polycythemic mice and the programmed isolated perfused canine kidney was investigated. Arachidonate in the lowest dose tested (50 microgram/kg i.p.) maximally stimulated erythropoiesis when administered to exhypoxic polycythemic mice. Kidneys from dogs made hypoxic for 4 hr at 0.42 atm pressure were perfused (2--3 ml/g/min, 37 degrees C) in a closed circuit system for 5 hr with blood from nonhypoxic donors. AA infusion (80 microgram/min) caused a significant (P less than .05) increase in erythropoietic activity of the perfusate as measured by the percentage of 48-hr 59Fe incorporation into red blood cells of exhypoxic polycythemic mice per milliliter of perfusate from an initial value of 1.66 +/- 0.50% to 6.05 +/- 0.96% over the 1st hr of infusion whereas vehicle controls showed no change. To determine whether this increase in Ep production was dependent on biosynthesis of renal prostaglandins and their intermediates, the ability of indomethacin to block AA-induced Ep production was studied. When kidney donors were twice pretreated with indomethacin 12 hr and immediately before their hypoxic exposure, no increase in Ep titers were seen during AA infusion. These results support the hypothesis that endogenously synthesized prostaglandins, their intermediates and/or other products of AA metabolism, such as prostacyclin and prostaglandins play an important role in the control Ep production.
研究了花生四烯酸（AA），即双烯前列腺素前体，在低氧性红细胞增多症小鼠和程序化离体灌注犬肾中刺激红细胞生成和促红细胞生成素（Ep）产生的能力。当给低氧性红细胞增多症小鼠注射测试的最低剂量（50微克/千克腹腔注射）的花生四烯酸盐时，可最大程度地刺激红细胞生成。将在0.42个大气压下低氧4小时的犬的肾脏在闭路系统中以2-3毫升/克/分钟、37摄氏度的速度用来自非低氧供体的血液灌注5小时。输注AA（80微克/分钟）导致灌注液的红细胞生成活性显著（P<0.05）增加，通过每毫升灌注液中48小时59Fe掺入低氧性红细胞增多症小鼠红细胞的百分比来衡量，在输注的第1小时内从初始值（1.66±0.50%）增加到6.05±0.96%，而载体对照组无变化。为了确定这种Ep产生的增加是否依赖于肾脏前列腺素及其中间体的生物合成，研究了吲哚美辛阻断AA诱导的Ep产生的能力。当肾脏供体在低氧暴露前12小时和立即进行两次吲哚美辛预处理时，在输注AA期间未观察到Ep滴度增加。这些结果支持这样的假设，即内源性合成的前列腺素、其中间体和/或AA代谢的其他产物，如前列环素和前列腺素在控制Ep产生中起重要作用。
