Contraction inhibition by β-agonists progressively decreases before labor in the rat myometrium

OBJECTIVE: This study tested the hypothesis that gestational age and agonist concentration are important determinants of β-adrenergic–dependent myometrial contraction inhibition. STUDY DESIGN: In vitro concentration-response curves for ritodrine and terbutaline were generated with myometrial strips collected from 21-day-pregnant rats. The in vitro efficacy of ritodrine (0.1 μmol/L) was evaluated in tissue from 15-, 18-, and 21-day animals. Contractile responses were analyzed by computer and normalized to a control potassium response. RESULTS: The degree of the inhibitory effects of both drugs was concentration dependent over the range of 0.01 to 10 μmol/L. The duration of contraction inhibition progressively decreased from 15 to 21 days of pregnancy. CONCLUSION: The degree of tachyphylaxis with β-agonists is dependent on and increases with the gestational age of the target tissue. β-Agonist type was not an important determinant of the duration of inhibitory response. We speculate that the effect of gestational age on tachyphylaxis may be related to increased myometrial expression of inactivating β-adrenergic receptor kinases. (AM J OBSTET GYNECOL 1996;174:1637-42.)