Naloxone potentiates epinephrine release during hypoxia in fetal sheep: dose response and cardiovascular effects

The effect of opiate receptor blockade on the plasma catecholamine response to hypoxemia was studied in seven chronically catheterized fetal lambs in utero. All animals underwent treatment with hypoxia alone, naloxone infusion alone (2 mg/kg) and hypoxia with naloxone at four different dosages (0.1, 0.5, 1.0, and 2.0 mg/kg). Maternal and fetal hypoxia was maintained for 20 min. There were no differences noted in the degree of hypoxemia or acidemia between the different hypoxia treatment groups. Hypoxia increased both norepinephrine and epinephrine plasma levels in all fetal sheep studied. We found a dose-dependent increase in plasma epinephrine levels in response to naloxone infusion during hypoxia. Plasma epinephrine level by 20 min of hypoxia with the 0.1 mg/kg naloxone dose (geometric mean 5366 pg/ml) was significantly more than with hypoxia alone (997 pg/ml). Naloxone at the other doses did not alter the epinephrine responses. There was no augmentation of plasma norepinephrine levels by naloxone at any dose studied. Thus, naloxone augmented the plasma epinephrine response to hypoxia in fetal sheep suggesting that the opiate peptides act as modulators of the sympathoadrenal system. The naloxone dose response differences observed in this study suggest this modulation is largely by antagonism of mu-receptors.