Effects of eicosanoids on the water and sodium balance of the neonate

Experimental and clinical evidence support the assumption that eicosanoids affect the morphological development and the functional behaviour of the kidney during the intra-uterine and newborn periods. Inhibition of prostaglandin (PG) synthesis in the pregnant rhesus monkey resulted in renal hypoplasia in the offspring. The plasma levels of PGs are high in the newborn. Production of PGE₂ by the cortical collecting duct was found to be similar in newborn and adult rabbit but the affinity of the renal tissue of the newborn for this eicosanoid was higher than that of the renal tissue of the adult rat. Based on findings in adult animals this would be expected to blunt the effect of antidiuretic hormone and account, in part, for the limited ability of the newborn to concentrate the urine. Yet, administration to unanaesthetized newborn rats of acetaminophen, a drug that inhibits the synthesis of PGE₂ and thromboxane B₂, blocked, rather than enhanced, the increment in urine osmolality produced by 1 h of water deprivation. The effect was absent in weaning and adult rats. A similar experimental manoeuvre increased sodium excretion in newborn but not in weaning or adult rats. Age-related differences are also evident with regard to side effects of PG synthesis inhibition. Whereas in adults adverse effects were reported only among patients with pre-existing renal disease, in newborns they occurred even after the administration of a single dose of inhibitor. Fortunately, the deleterious effects of PG synthesis inhibition on renal function appear to be reversible.