AJP - Endocrinology and Metabolism, Vol 253, Issue 4 E410-E417, Copyright © 1987 by American Physiological Society
Myometrial desensitization after ritodrine infusion
S. N. Caritis, J. P. Chiao, J. J. Moore and S. M. Ward
Department of Obstetrics and Gynecology, University of Pittsburgh School of Medicine, Magee-Womens Hospital, Pennsylvania 15123.
We have developed a model in pregnant sheep to investigate pharmacological
agents used for suppression of preterm labor. This model allows repetitive
determinations of uterine contractility and simultaneous measurements of
myometrial receptor and postreceptor events. We used the model to study the
beta-adrenergic agent ritodrine. We infused 11 pregnant sheep with
ritodrine and 3 with physiological saline for 24 h. Oxytocin boluses were
given before and at 5 and 22 h after onset of the infusion. Myometrial
biopsies were obtained before and immediately after the infusion. After 22
h of ritodrine infusion, uterine contractility in response to the same
oxytocin bolus was 50% greater than at 5 h (P less than 0.02). Myometrial
membrane beta-adrenergic receptor density decreased 49% (P less than
0.005), and catecholamine-stimulated adenylate cyclase activity was reduced
70% (P less than 0.005). The model thus demonstrates that use of the
beta-adrenergic agonist ritodrine in a clinically relevant manner results
in tachyphylaxis of its effects on both physiological parameters and the
receptor cascade system.
