Dexamethasone effects on ritodrine-induced changes in myometrial contractility and beta-adrenergic receptor function.
We have previously demonstrated in pregnant sheep that ritodrine infusion for 24 hours reduces myometrial beta-adrenergic receptor density and isoproterenol-stimulated adenylate cyclase activity. These receptor-associated changes were accompanied by an increasing inability of ritodrine to inhibit uterine contractility induced by a bolus of oxytocin. In the present study, we evaluated whether these ritodrine-induced effects could be altered by dexamethasone. Ten pregnant sheep at gestational ages of 92 to 130 days received ritodrine 2 micrograms/kg/min for 24 hours. Five animals also received dexamethasone 10 mg intravascularly twice during the ritodrine infusion. Before and at 4 and 24 hours of ritodrine infusion, the animals were given an identical dose of oxytocin as a bolus, and the area under the uterine pressure-time curve was quantified. Myometrial biopsy specimens were obtained before and after ritodrine infusion. Dexamethasone treatment prevented ritodrine-induced reductions in beta-adrenergic receptor density and isoproterenol-stimulated adenylate cyclase activity. Despite these receptor-associated effects, dexamethasone did not prevent the loss of tocolytic efficacy associated with prolonged ritodrine infusion.
Ward
S M
SM
Department of Obstetrics and Gynecology, University of Pittsburgh School of Medicine, Magee-Womens Hospital, PA 15213.
Caritis
S N
SN
Chiao
J P
JP
Moore
J J
JJ
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D009215:Myometrium / Q000378:metabolism*; D010121:Oxytocin / Q000494:pharmacology; D011247:Pregnancy; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D012312:Ritodrine / Q000494:pharmacology*; D012756:Sheep; D014590:Uterine Contraction / Q000187:drug effects*
D011943:Receptors, Adrenergic, beta; D010121:Oxytocin; D003907:Dexamethasone; D012312:Ritodrine