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-mu-g/kg every 1.5 hours, whereas five other animals received ritodrine as a continuous infusion of 0.18-mu-g/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.