EFFECTS OF ARACHIDONIC-ACID ON ERYTHROPOIETIN PRODUCTION IN EXHYPOXIC POLYCYTHEMIC MICE AND ISOLATED PERFUSED CANINE KIDNEY

  • 1 January 1978
    • journal article
    • research article
    • Vol. 207  (2) , 402-409
Abstract
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 .mu.g/kg i.p.) maximally stimulated erythropoiesis when administered to exhypoxic polycythemic mice. Kidneys from dogs made hypoxic for 4 h at 0.42 atm pressure were perfused (2-3 ml/g per min, 37.degree. C) in a closed circuit system for 5 h with blood from nonhypoxic donors. AA infusion (80 .mu.g/min) caused a significant (P < .05) increased in erythropoietic activity of the perfusate, measured by the percentage of 48 h 59Fe incorporation into red blood cells of exhypoxic polycythemic mice/ml of perfusate from an initial value of 1.66 .+-. 0.50% to 6.05 .+-. 0.96% over the 1st h of infusion. 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 h and immediately before their hypoxic exposure, no increase in Ep titers was seen during AA infusion. Endogenously synthesized prostaglandsin, their intermediates and/or other products of AA metabolism, e.g., prostacyclin and prostaglands, play an important role in the control of Ep production.