Effects of inhibition of prostaglandin synthesis on fetal renal function

Abstract

The role of renal prostaglandin production on the control of renal blood flow (RBF) and renal function was studied in eight chronically catheterized fetal lambs during the last trimester of gestation by using indomethacin as an inhibitor of prostaglandin synthesis. Following administration of indomethacin, RBF decreased significantly (-7.44 ± 2.04 ml/min) whereas significant increases in filtration fraction (+3.92 ± 0.85%) and renal vascular resistance (+0.41 ± 0.13 mm Hg · ml-1 ≥ min -1) were observed. Significant changes in glomerular perfusion rate were observed only in the inner portion of the cortex. No changes in GFR were demonstrated. Following administration of indomethacin, significant increases in fetal urinary sodium (+22.2 ± 7.03 μEq/min) and chloride excretion (+ 18.2 ± 6.26 μEq/min) were found despite a decrease in RBF. No changes in potassium excretion were seen. A significant increase in U(Osm) (+100 ± 25.9 mOsm/kg H2O) not associated with significant changes in urinary flow rate was also demonstrated following indomethacin. Finally, fetal administration of indomethacin produced a significant decrease in plasma renin activity (-2.70 ± 0.65 ng/ml/hr) not associated with changes in plasma aldosterone concentration. The present data are consistent with the idea that prostaglandins are important modulators of RBF and renin secretion during fetal life. The inability of indomethacin to render the urine hypertonic indicates that the inability of the fetal kidney to concentrate is probably not due to endogenous activity of the renal prostaglandin system. The increase in sodium chloride excretion with a concomitant reduction of RBF is a pattern not previously reported following inhibition of prostaglandin production. In addition to their effects on RBF and renin release, renal prostaglandins in the fetal kidney may have tubular effects on sodium and chloride absorption that are opposite to those generally ascribed to adult kidneys.