Myometrial desensitization after ritodrine infusion

We have developed a model in pregnant sheep to investigate pharmacological agents used for suppression of preterm labor. This model allows repetitive determinations of uterine contractility and simultaneous measurements of myometrial receptor and postreceptor events. We used the model to study the beta-adrenergic agent ritodrine. We infused 11 pregnant sheep with ritodrine and 3 with physiological saline for 24 h. Oxytocin boluses were given before and at 5 and 22 h after onset of the infusion. Myometrial biopsies were obtained before and immediately after the infusion. After 22 h of ritodrine infusion, uterine contractility in response to the same oxytocin bolus was 50% greater than at 5 h (P less than 0.02). Myometrial membrane beta-adrenergic receptor density decreased 49% (P less than 0.005), and catecholamine-stimulated adenylate cyclase activity was reduced 70% (P less than 0.005). The model thus demonstrates that use of the beta-adrenergic agonist ritodrine in a clinically relevant manner results in tachyphylaxis of its effects on both physiological parameters and the receptor cascade system.