Indomethacin-induced urinary flow rate reduction in the ovine fetus is associated with reduced free water clearance and elevated plasma arginine vasopressin levels.
OBJECTIVE
The purpose of our study was to explore the urinary responses of the ovine fetus to indomethacin levels comparable with those used therapeutically in the human fetus.


METHODS
After a 1-hour control period, chronically catheterized ovine fetuses between 125 and 139 days of gestation were given an intravenous bolus of indomethacin (0.05 mg/kg estimated fetal weight) followed by a 0.0025 mg/kg/min continuous infusion for 5 hours. The experimental group (n = 9) was compared with a vehicle-only infusion group (n = 10).


RESULTS
There was a sustained 55.7% +/- 9.5% (mean +/- SEM) decrease in urinary output by 2 hours of indomethacin infusion (p < 0.00001, analysis of variance). Urinary osmolality, potassium, and chloride concentrations underwent sustained increases during the infusion period (p < 0.005). Free water clearance decreased by 67.5% +/- 12.0% (p < 0.001). Fetal arterial pressure increased only transiently (p < 0.05), and increases in venous pressure (p = 0.013) and heart rate (p < 0.0001) were sustained. Fetal plasma arginine vasopressin concentration increased during indomethacin infusion (p < 0.05) and was correlated with the fall in urinary flow rate and free water clearance (p = 0.002). During vehicle infusion no significant changes were observed in any of the variables.


CONCLUSIONS
Our data indicate that the fetus undergoes antidiuresis when exposed to low levels of indomethacin and that the observed antidiuresis is mediated by a decrease in free water clearance. The reduction in free water clearance may be mediated by increases in plasma arginine vasopressin concentrations.
Walker
M P
MP
Department of Reproductive Medicine, University of California, San Diego, La Jolla 92093-0802.
Moore
T R
TR
Cheung
C Y
CY
Brace
R A
RA
D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood*; D009320:Atrial Natriuretic Factor / Q000097:blood; D004231:Diuresis / Q000187:drug effects*; D005333:Fetus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology*; D015999:Multivariate Analysis; D012756:Sheep; D014556:Urine / Q000737:chemistry; D014867:Water / Q000378:metabolism*
D014867:Water; D001127:Arginine Vasopressin; D009320:Atrial Natriuretic Factor; D007213:Indomethacin