THE ROLE OF ENDOTHELIN-A RECEPTORS IN CARDIOVASCULAR-RESPONSES TO ACUTE HYPOXEMIA IN THE LATE-GESTATION SHEEP FETUS

1. In unanaesthetized chronically instumented fetal sheep (118-121 day s gestation) we investigated the effect of acute isocapnic hypoxaemia (arterial P-O2, 12.5 +/- 0.6 mmHg) on heart rate (FHR), mean systemic arterial blood pressure (MABP), carotid and femoral blood flows (CBF a nd FBF, respectively), and carotid and femoral vascular resistances (C VR and FVR, respectively) with the infusion of either the endothelin-A (ETA) receptor antagonist FR139317, or saline vehicle. 2. During norm oxaemia FHR (P < 0.05) and CBP (P < 0.01) were greater, and CVR (P < 0 .01) was lower with FR139317 than with vehicle infusion. CVR remained lower with FR139317 than with vehicle infusion during hypoxaemia (P < 0.01) and recovery (P < 0.05). During hypoxaemia the rapid initial bra dycardia, the increase in MABP and FVR and the decrease in FBF were si milar with vehicle and FR139317 infusion. In both groups plasma endoth elin-1 concentration ([ET-1]) was unaltered by hypoxaemia. The increas e in CBF during hypoxaemia with vehicle (P < 0.01) was absent with FR1 39317 infusion. 3. Thus in the late gestation ovine fetus endogenous E T-1 modulates basal FHR, CBF and CVR via ETA receptors. Modulation of CBF and CVR persists during hypoxaemia but ETA receptors do not appear to contribute to the decrease in femoral blood flow measured during a cute hypoxaemia.