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Myometrial desensitization after ritodrine infusion.
S N Caritis1, J P Chiao, J J Moore
1Department of Obstetrics and Gynecology, University of Pittsburgh School of Medicine, Magee-Womens Hospital, Pennsylvania 15123.
The American Journal of Physiology
|October 1, 1987
Summary
Ritodrine, a beta-adrenergic agonist, was studied in pregnant sheep to assess preterm labor suppression. The study found that prolonged ritodrine use leads to tachyphylaxis, reducing its effectiveness on uterine contractility and the receptor system.
Area of Science:
- Pharmacology
- Reproductive Biology
- Obstetrics
Background:
- Preterm labor remains a significant concern in perinatal medicine.
- Pharmacological agents are used to suppress uterine contractions.
- Understanding the mechanisms of tocolytic agent efficacy and limitations is crucial.
Purpose of the Study:
- To develop and utilize a pregnant sheep model for investigating pharmacological agents targeting preterm labor.
- To examine the effects of the beta-adrenergic agonist ritodrine on uterine contractility and myometrial events.
- To assess the development of tachyphylaxis with sustained ritodrine administration.
Main Methods:
- A pregnant sheep model was employed to study uterine contractility and myometrial responses.
- Ritodrine was infused into pregnant sheep for 24 hours, with oxytocin challenges administered at intervals.
- Myometrial biopsies were collected to analyze beta-adrenergic receptor density and adenylate cyclase activity.
Main Results:
- Sustained ritodrine infusion resulted in a 50% increase in uterine contractility in response to oxytocin after 22 hours.
- Myometrial beta-adrenergic receptor density decreased by 49% with ritodrine treatment.
- Catecholamine-stimulated adenylate cyclase activity was reduced by 70% following ritodrine infusion.
Conclusions:
- The developed pregnant sheep model effectively demonstrates tachyphylaxis to ritodrine.
- Clinically relevant ritodrine administration leads to diminished efficacy due to receptor and postreceptor desensitization.
- This study highlights the limitations of beta-adrenergic agonists in long-term preterm labor suppression.