THE EFFECT OF METYRAPONE INFUSION ON ARTERIAL BLOOD PRESSURE IN THE LATE GESTATION FETAL SHEEP

K.E. Warnes, C.L. Coulter, J.S. Robinson, I.C. McMillen, Department of Physiology and Department of Obstetrics and Gynaecology, University of Adelaide, Adelaide, South Australia

Exposure of the fetus to excess glucocorticoids is known to significantly increase fetal arterial blood pressure. In addition there is an increase in fetal blood pressure over the last month of gestation, concomitantly with a rise in circulating fetal plasma cortisol concentrations. However, the role of endogenous cortisol in the maintenance of fetal arterial blood pressure is unclear. The aim of this study was to determine the effect of suppression of endogenous cortisol concentrations on fetal arterial blood pressure during late gestation. Surgery was performed at 119-120d on seven pregnant ewes to insert vascular catheters into the fetus and ewe for infusion studies and collection of blood samples for hormone analysis, before the experiment and during the experimental period. To suppress fetal cortisol synthesis, Metyrapone (6µmoles/h; a competitive inhibitor of 11β hydroxylase n=7) was infused into the fetal jugular vein from 137d gestation until 140d (term = 147± 3 d). Fetal arterial blood pressure was measured directly via the fetal carotid artery continuously from 137d (180 min prior to infusion) until +6h after the start of the infusion. Metyrapone infusion caused a decrease in fetal cortisol concentrations at 6 h after the start of infusion (12.8 ± 3.3 nmol.L^-1 compared with 5.8 ± 1.3 nmol.L^-1). There was also an increase in fetal ACTH concentrations at 6h after the start of infusion when compared to pre infusion concentrations (87.4 ± 6.3 pg.ml^-1 compared with 283.1 ± 51.4 pg.ml^-1). There was however, no significant change in fetal arterial blood pressure with metyrapone infusion (46.9 ± 1.2 mmHg compared with 47.9 ± 1.8 mmHg). These data suggest that during late gestation cortisol concentrations may not play a role in the maintenance of basal fetal arterial blood pressure.