Failure of ritodrine to prevent preterm labor in the sheep.
OBJECTIVE
The purpose of this study was to determine whether continuous infusion of ritodrine could prevent preterm delivery in sheep.


METHODS
Sheep in preterm labor induced by RU 486 (mifepristone) received infusions of either ritodrine (n = 5) or saline solution (n = 5), and the progress of labor was monitored. beta 2-Adrenergic receptor density and function (agonist-induced cyclic adenosine monophosphate production) was measured in myometrial samples from both groups.


RESULTS
Ritodrine initially inhibited labor contractions. This inhibition was only maintained for 16 hours, after which both the amplitude and frequency of electromyographic bursts and contractions returned. The failure of the myometrium to respond to ritodrine (desensitization) was associated with significant reductions in agonist-induced cyclic adenosine monophosphate production and beta 2-adrenergic receptor concentration in myometrial tissue collected from these animals compared with the saline solution-treated controls.


CONCLUSIONS
Continuous infusion of ritodrine to sheep in preterm labor produces only a transient inhibition of contractions. This desensitization is caused by a down-regulation of myometrial beta 2-adrenergic receptors.
Lye
S J
SJ
Division of Perinatology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Dayes
B A
BA
Freitag
C L
CL
Brooks
J
J
Casper
R F
RF
D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis; D003864:Depression, Chemical; D015536:Down-Regulation; D005260:Female; D005324:Fetal Movement / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006340:Heart Rate, Fetal / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism; D007752:Obstetric Labor, Premature / Q000378:metabolism / Q000517:prevention & control*; D011247:Pregnancy; D011453:Prostaglandins / Q000097:blood; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D012119:Respiration / Q000187:drug effects; D012312:Ritodrine / Q000627:therapeutic use*; D012756:Sheep; D014590:Uterine Contraction / Q000187:drug effects
D011453:Prostaglandins; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D012312:Ritodrine; D007545:Isoproterenol