Cardiovascular effects of a μ-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-phenylalanine-lysine-NH2), a μ-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 methiodide (6 mg/h); it was also given in conjunction with the β-adrenergic antagonist propranolol (2 mg/h). Statistical analyses were performed by 1-way and 2-way analysis of variance. Results: The fetus responded to DALDA with an increase in heart rate with all doses (P< .01) but without any change in blood pressure. This response was abolished by naloxone (P< .001), naloxone methiodide (P = .003), and propranolol (P< .001). Conclusions: In the fetus intravenous DALDA increases heart rate without any change in blood pressure by way of the μ receptor and through central sympathetic activation. These effects of DALDA are different from those seen in the adult, suggesting different sites and mechanisms of action. (Am J Obstet Gynecol 1999;180:1127-30.)