The role of endothelin-A receptors in cardiovascular responses to acute hypoxaemia in the late gestation sheep fetus.

1. In unanaesthetized chronically instumented fetal sheep (118-121 days gestation) we investigated the effect of acute isocapnic hypoxaemia (arterial Po2, 12.5 +/- 0.6 mmHg) on heart rate (FHR), mean systemic arterial blood pressure (MABP), carotid and femoral blood flows (CBF and FBF, respectively), and carotid and femoral vascular resistances (CVR and FVR, respectively) with the infusion of either the endothelin-A (ETA) receptor antagonist FR139317, or saline vehicle. 2. During normoxaemia FHR (P < 0.05) and CBF (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 bradycardia, the increase in MABP and FVR and the decrease in FBF were similar with vehicle and FR139317 infusion. In both groups plasma endothelin-1 concentration ([ET-1]) was unaltered by hypoxaemia. The increase in CBF during hypoxaemia with vehicle (P < 0.01) was absent with FR139317 infusion. 3. Thus in the late gestation ovine fetus endogenous ET-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 acute hypoxaemia.