Effects of inhibition of prostaglandin synthesis on fetal renal function

Effects of inhibition of prostaglandin synthesis on the fetal renal function. 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 H 2 O) 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. Effets de l'inhibition de la synthese de prostaglandine sur la fonction renale du foetus. Le role de la production renale de prostaglandine sur le controle du debit sanguin renal et de la fonction renale a ete etudie chez 8 agneaux catheterises de facon chronique pendant le dernier trimestre de la gestation en utilisant l'indomethacine comme inhibiteur de la synthese de prostaglandine. Apres l'administration d'indomethacine, le debit sanguin renal diminue significativement (-7.44 ± 2,04 ml/min) en meme temps que des augmentations significatives de la fraction filtree ( + 3,92 ± 0,85%) et de la resistance vasculaire renale sont observees (0,41 ± 0,13 mm Hg · ml -1 ' · min -1 ). Des modifications significatives du debit de perfusion glomerulaire n'ont ete observees que dans la partie profonde du cortex. Il n'a pas ete mis en evidence de diminution du debit de filtration glomerulaire. Apres â administration d'indomethacine, une augmentation significative de l'excretion urinaire de sodium ( + 22,2 ± 7,03 µEq/min) et de chlore (+18,2 ± 6.26 µEq/min) a ete observee malgre la diminution du debit sanguin renal. Il n'a pas ete constate d'augmentation de l'excretion du potassium. Une augmentation significative de U Osm (+ 100 + 25,9 mOsm/kg H 2 O) non associee a des modifications significatives du debit urinaire a aussi ete mise en evidence apres l'administration d'indomethacine. Enfin, l'administration d'indomethacine au foetus a produit une diminution significative de l'activite renine plasmatique (-2.70 ± 0,65 ng/ml/hr) non associee a une modification de la concentration plasmatique d'aldosterone. Les resultats sont en accord avec l'idee selon laquelle les prostaglandines seraient des modulateurs importants du debit sanguin renal et de la secretion de renine au cours de la vie foetale. L'incapacite de l'indomethacine a rendre l'urine hypertonique indique que l'incapacite a concentrer du rein foetal n'est probablement pas liee a l'activite endogene du systeme de prostaglandine renal. L'augmentation de l'excretion renale de chlorure de sodium en meme temps que le debit sanguin renal diminue est une modalite qui n'a pas ete rapportee jusqu'ici a la suite de l'inhibition de la production de prostaglandine. En plus de leurs effets sur le debit sanguin renal et la liberation de renine, les prostaglandines renales du rein foetal peuvent avoir des effets tubulaires sur l'absorption de sodium et de chlorure a l'oppose de ceux generalement decrits pour le rein adulte.