Comparison of pulsatile and continuous ritodrine administration: effects on uterine contractility and beta-adrenergic receptor cascade.
In this study we compare the uterine contractility and beta-adrenergic receptor effects of identical doses of ritodrine administered intermittently or continuously for 24 hours in pregnant sheep. Ritodrine was administered intravenously to five animals as a pulse, 16 micrograms/kg every 1.5 hours, whereas five other animals received ritodrine as a continuous infusion of 0.18 microgram/kg/min. Ritodrine plasma concentrations at steady state were comparable in both groups and averaged 18 ng/ml. Animals receiving ritodrine pulses demonstrated no alteration of myometrial beta-adrenergic receptors or adenylyl cyclase activity, and ritodrine inhibited oxytocin-induced contractility comparably at 4 and 24 hours. Animals receiving ritodrine continuously had a significant decrease in myometrial beta-adrenergic receptors and adenylyl cyclase activity, yet ritodrine inhibition of oxytocin-induced uterine contractility was sustained for 24 hours. Oxytocin receptors were not affected by ritodrine administration and were similar in both groups. At the dose studied, oxytocin-induced contractions are comparably inhibited by ritodrine for 24 hours whether the drug is given continuously or in a pulsatile fashion.
Caritis
S N
SN
Department of Obstetrics and Gynecology, University of Pittsburgh School of Medicine, Magee-Womens Hospital, PA 15213.
Chiao
J P
JP
Kridgen
P
P
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D004789:Enzyme Activation; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D009215:Myometrium / Q000378:metabolism; D009994:Osmolar Concentration; D010121:Oxytocin / Q000494:pharmacology; D011673:Pulsatile Flow; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D012312:Ritodrine / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D012756:Sheep; D014590:Uterine Contraction / Q000187:drug effects*
D011943:Receptors, Adrenergic, beta; D010121:Oxytocin; D000262:Adenylyl Cyclases; D012312:Ritodrine; D007545:Isoproterenol