CONTRACTION INHIBITION BY BETA-AGONISTS PROGRESSIVELY DECREASES BEFORE LABOR IN THE RAT MYOMETRIUM

OBJECTIVE: This study tested the hypothesis that gestational age and a gonist concentration are important determinants of beta-adrenergic-dep endent myometrial contraction inhibition. STUDY DESIGN: In vitro conce ntration-response curves for ritodrine and terbutaline were generated with myometrial strips collected from 21-day-pregnant rats. The in vit ro efficacy of ritodrine (0.1 mu mol/L) was evaluated in tissue from 1 5-, 18-, and 21-day animals. Contractile responses were analyzed by co mputer and normalized to a control potassium response. RESULTS: The de gree of the inhibitory effects of both drugs was concentration depende nt over the range of 0.01 to 10 mu mol/L. The duration of contraction inhibition progressively decreased from 15 to 21 days of pregnancy. CO NCLUSION: The degree of tachyphylaxis with beta-agonists is dependent on and increases with the gestational age of the target tissue. beta-A gonist type was not an important determinant of the duration of inhibi tory response. We speculate that the effect of gestational age on tach yphylaxis may be related to increased myometrial expression of inactiv ating beta-adrenergic receptor kinases.