Contraction inhibition by beta-agonists progressively decreases before labor in the rat myometrium.
OBJECTIVE
This study tested the hypothesis that gestational age and agonist concentration are important determinants of beta-adrenergic-dependent myometrial contraction inhibition.


METHODS
In vitro concentration-response curves for ritodrine and terbutaline were generated with myometrial strips collected from 21-day-pregnant rats. The in vitro efficacy of ritodrine (0.1 mumol/L) was evaluated in tissue from 15-, 18-, and 21-day animals. Contractile responses were analyzed by computer and normalized to a control potassium response.


RESULTS
The degree of the inhibitory effects of both drugs was concentration dependent over the range of 0.01 to 10 mumol/L. The duration of contraction inhibition progressively decreased from 15 to 21 days of pregnancy.


CONCLUSIONS
The degree of tachyphylaxis with beta-agonists is dependent on and increases with the gestational age of the target tissue. beta-Agonist type was not an important determinant of the duration of inhibitory response. We speculate that the effect of gestational age on tachyphylaxis may be related to increased myometrial expression of inactivating beta-adrenergic receptor kinases.
Yeagley
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Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, PA, USA.
Caritis
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Ruzycky
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D005260:Female; D005865:Gestational Age; D066298:In Vitro Techniques; D007743:Labor, Obstetric / Q000502:physiology*; D009994:Osmolar Concentration; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012312:Ritodrine / Q000494:pharmacology; D013618:Tachyphylaxis; D013726:Terbutaline / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D012312:Ritodrine; D013726:Terbutaline