Indomethacin-induced urinary flow rate reduction in the ovine fetus is associated with reduced free water clearance and elevated plasma arginine vasopressin levels

Martin P.R. Walker, Thomas R. Moore, Cecilia Y. Cheung, Robert A. Brace

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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. STUDY DESIGN: 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.

Original languageEnglish (US)
Pages (from-to)1723-1731
Number of pages9
JournalAmerican journal of obstetrics and gynecology
Volume167
Issue number6
DOIs
StatePublished - Dec 1992

Keywords

  • Sheep
  • free water clearance
  • indomethacin
  • prostaglandins
  • urinary flow
  • venous pressure

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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