Laboratory Investigation

Kidney International (1981) 20, 621–627; doi:10.1038/ki.1981.185

Effects of inhibition of prostaglandin synthesis on fetal renal function

James R Matson1, John B Stokes1 and Jean E Robillard1

1Departments of Pediatrics and Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa

Correspondence: Dr J E Robillard, Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, Iowa, 52242, USA

Received 19 January 1981; Revised 17 March 1981.

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Abstract

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 plusminus 2.04 ml/min) whereas significant increases in filtration fraction ( + 3.92 plusminus 0.85%) and renal vascular resistance ( + 0.41 plusminus 0,13 mm Hg dot ml-1 dot 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 plusminus 7.03 microEq/min) and chloride excretion (+18.2 plusminus 6.26 microEq/min) were found despite a decrease in RBF. No changes in potassium excretion were seen. A significant increase in UOsm (+ 100 plusminus 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 plusminus 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 synthèse de prostaglandine sur la fonction rénale du foetus. Le rôle de la production rénale de prostaglandine sur le contrôle du débit sanguin rénal et de la fonction rénale a été étudié chez 8 agneaux cathétérisés de façon chronique pendant le dernier trimestre de la gestation en utilisant l'indométhacine comme inhibiteur de la synthèse de prostaglandine. Après l'administration d'indométhacine, le débit sanguin rénal diminue significativement (-7.44 plusminus 2,04 ml/min) en même temps que des augmentations significatives de la fraction filtrée ( + 3,92 plusminus 0,85%) et de la résistance vasculaire rénale sont observées (0,41 plusminus 0,13 mm Hg dot ml -1' dot min -1). Des modifications significatives du débit de perfusion glomérulaire n'ont été observées que dans la partie profonde du cortex. Il n'a pas été mis en évidence de diminution du débit de filtration glomérulaire. Après â administration d'indométhacine, une augmentation significative de l'excrétion urinaire de sodium ( + 22,2 plusminus 7,03 microEq/min) et de chlore (+18,2 plusminus 6.26 microEq/min) a été observée malgré la diminution du débit sanguin rénal. Il n'a pas été constaté d'augmentation de l'excrétion du potassium. Une augmentation significative de UOsm (+ 100 + 25,9 mOsm/kg H2O) non associée à des modifications significatives du débit urinaire a aussi été mise en évidence après l'administration d'indométhacine. Enfin, l'administration d'indométhacine au foetus a produit une diminution significative de l'activité rénine plasmatique (-2.70 plusminus 0,65 ng/ml/hr) non associée à une modification de la concentration plasmatique d'aldostérone. Les résultats sont en accord avec l'idée selon laquelle les prostaglandines seraient des modulateurs importants du débit sanguin rénal et de la sécrétion de rénine au cours de la vie foetale. L'incapacité de l'indométhacine à rendre l'urine hypertonique indique que l'incapacité à concentrer du rein foetal n'est probablement pas liée à l'activité endogène du système de prostaglandine rénal. L'augmentation de l'excrétion rénale de chlorure de sodium en même temps que le débit sanguin rénal diminue est une modalité qui n'a pas été rapportée jusqu'ici à la suite de l'inhibition de la production de prostaglandine. En plus de leurs effets sur le débit sanguin rénal et la libération de rénine, les prostaglandines rénales du rein foetal peuvent avoir des effets tubulaires sur l'absorption de sodium et de chlorure à l'opposé de ceux généralement décrits pour le rein adulte.

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