β2- and β3-Adrenoreceptor agonists: Human myometrial selectivity and effects on umbilical artery tone

Objective: The purpose of this study was to investigate the functional selectivity of the β3-adrenoreceptor agonist BRL 37344 and the β2-adrenoreceptor agonist ritodrine for their putative receptors in human pregnant myometrium in vitro and to examine the possibility that BRL 37344 may exert an effect on other β-adrenoreceptor subtypes. This study also aimed comparatively to evaluate the in vitro effects of BRL 37344 and ritodrine on human vascular tissue tone. Study Design: The effects of BRL 37344 (1 nmol/L–100 μmol/L) and ritodrine (1 nmol/L–100 μmol/L) on isometric tension recordings that were performed in isolated myometrial strips that were obtained at elective cesarean delivery and in human umbilical artery rings that were obtained at term were measured. Antagonism of the effects of BRL 37344 and ritodrine in human myometrial tissue was investigated with the antagonists butoxamine (1 μmol/L), propranolol (1 μmol/L), and bupranolol (1 μmol/L). The concentrations that produced a 50% maximal effect, the mean maximal inhibition that was achieved, and the percentage of contractility that was observed were compared. Results: Bupranolol (n = 6), but not butoxamine (n = 6) or propranolol (n = 6), antagonized the relaxant effects of BRL 37344 in human pregnant myometrium; all three compounds (n = 6, respectively) antagonized the effects of ritodrine. At concentrations of >1 μmol/L, ritodrine exerted a significantly more potent vasodilatory effect than BRL 37344 on human umbilical artery tone (P< .01). Conclusion: The relaxant effects of BRL 37344 appear to be mediated solely through the β3-adrenoreceptor agonist, although ritodrine may exert an effect on β1-, β2-, and β3-adrenoreceptor agonists. This and the reduction in vascular tissue effects observed with BRL 37344 suggest that uterine β3-adrenoreceptor modulation may provide a novel scientific approach to tocolysis with fewer vascular adverse effects. (Am J Obstet Gynecol 2002;187:641-7.)