Cardiovascular effects of a mu-selective opioid agonist (tyrosine-D-arginine-phenylalanine-lysine-NH2) in fetal sheep: Sites and mechanisms of action

OBJECTIVE: We investigated the effects of DALDA (tyrosine-D-arginine-phenyl alanine-lysine-NH2), a mu-selective opioid peptide, on heart rate and blood pressure in fetal sheep with long-term instrument implantation. STUDY DESIGN: DALDA was given as an intravenous bolus in doses ranging from 0.15 to 0.5 mg/kg. A 0.5 mg/kg dose of DALDA was given in the presence of the opioid antagonist naloxone and its quaternary analog naloxone methiodid e (6 mg/h); it was also given in conjunction with the beta-adrenergic antag onist propranolol (2 mg/h). Statistical analyses were performed by 1-way an d 2-way analysis of variance. RESULTS: The fetus responded to DALDA with an increase in heart rate with a ll doses (P <.01) but without any change in blood pressure. This response w as abolished by naloxone (P <.001), naloxone methiodide (P =.003), and prop ranolol (P <.001). CONCLUSIONS: In the fetus intravenous DALDA increases heart rate without an y change in blood pressure by way of the mu receptor and through central sy mpathetic activation. These effects of DALDA are different from those seen in the adult, suggesting different sites and mechanisms of action.