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-phenylalanine-lysine-NH2), a mu-selective opioid peptide, on heart rate and blood pressure in fetal sheep with long-term instrument implantation.


METHODS
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 beta-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 mu 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.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002319:Cardiovascular System / Q000187:drug effects / Q000196:embryology*; D005260:Female; D006340:Heart Rate, Fetal / Q000187:drug effects*; D007700:Kinetics; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D011247:Pregnancy; D011433:Propranolol / Q000494:pharmacology; D017450:Receptors, Opioid, mu / Q000819:agonists*; D012756:Sheep