Our aim was to characterize the pattern of release of epinephrine, norepinephrine, arginine vasopressin (AVP), cortisol (hydrocortisone), and prostaglandin E2 (PGE2) into the fetal circulation during prolonged reductions in uterine blood flow (RUBF). In five sheep RUBF was induced for 24 h, whereas in another five sheep (controls) uterine blood flow was not reduced. Fetal arterial oxygen saturation was decreased from 60.5 +/- 3.6 to 20.3 +/- 1.6% after 2 h of RUBF and remained significantly reduced for the entire RUBF period. The incidence of fetal breathing movements (FBM) and fetal arterial pH were reduced from 36.7 +/- 4.5 min/h and 7.36 +/- 0.01 to 4.3 +/- 1.8 min/h and 7.13 +/- 0.02, respectively, after 2 h of RUBF, but both had returned to control levels after 14 h. Fetal plasma AVP and epinephrine concentrations were increased from 4.4 +/- 0.5 pg/ml and 0.19 +/- 0.05 ng/ml to 333.8 +/- 41.5 pg/ml and 1.5 +/- 0.6 ng/ml, respectively, after 2 h and then declined to near control levels after 12 h of RUBF. Fetal plasma norepinephrine and cortisol concentrations were increased from 1.3 +/- 0.4 and 4.0 +/- 2.2 ng/ml to 6.1 +/- 1.8 and 13.5 +/- 4.1 ng/ml, respectively, after 2 h of RUBF, and both remained significantly elevated throughout the remainder of the RUBF period. Fetal plasma PGE2 concentrations progressively increased (from 1.9 +/- 0.4 to 8.8 +/- 1.7 nmol/l at 12 h) as the duration of RUBF increased and were still significantly elevated after 24 h. The time course for the increase in PGE2 during RUBF was very similar to the increases in arterial pH and in the incidence of FBM.(ABSTRACT TRUNCATED AT 250 WORDS)