Effect of Oxytocin Receptor and β2-Adrenoceptor Blockade on Myometrial Oxytocin Receptors in Parturient Rats1

Jan 23, 1999Biology of reproduction

How blocking oxytocin and stress hormone receptors affects oxytocin receptors in the uterus during labor in rats

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Abstract

In vivo infusion of the beta2-adrenoceptor antagonist ICI-118.551 in late pregnant rats prevented the rise in myometrial oxytocin receptor binding normally seen during delivery.

A reduced responsiveness of uterine strips to oxytocin was observed during labor after beta2AR blockade.
Treatment with the OTR antagonist atosiban down-regulated OTR binding sites in myometrium and impaired contractile response to oxytocin, without affecting gestational length.
Neither atosiban nor ICI-118.551 alone changed fetal mortality rates, but the combination significantly increased the incidence of fetal deaths.
The combination treatment also resulted in down-regulation of myometrial OTR and weakened contractile responses to oxytocin.
The findings suggest that the rise in OTR may not be essential for normal parturition outcomes, although it could play a role in preterm labor.

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It has been proposed that the rise in myometrial oxytocin receptor (OTR) concentrations at term triggers parturition. In the present study, we have shown that in vivo infusion of the beta2-adrenoceptor (beta2AR) antagonist ICI-118.551 in late pregnant rats prevents the rise in myometrial OTR binding normally seen during delivery. A reduced contractile responsiveness of uterine strips isolated from rats in labor when challenged with oxytocin (OT) and a slight shortening of gestation accompanied this effect. OTR mRNA levels were, however, unaltered after the treatment, suggesting that the effect of beta2AR blockade on myometrial OTR was posttranscriptional or due to influences on extra-myometrial tissue. Infusion of the OTR antagonist atosiban down-regulated OTR binding sites in the parturient myometrium and resulted in an impaired contractile response to OT without affecting gestational length. OTR gene expression did not change, as seen from unchanged OTR mRNA values. Neither atosiban nor ICI-118.551 infusions alone changed fetal mortality. A significant increase in the incidence of fetal deaths was found, however, when rats were treated with a combination of atosiban and ICI-118.551. This treatment also down-regulated myometrial OTR and weakened the contractile response to OT, but it did not change gestational length. We conclude that the timing and onset of a normal parturition as well as a favorable outcome seem to be independent of a rise in OTR. This fact cannot exclude the possibility that an increase in OTR is of importance in the genesis of preterm labor. We suggest that beta2 stimulation up-regulates OTR during delivery. This effect may partly be responsible for the tachyphylaxis seen after the use of beta2 agonists to control preterm labor. We further suggest that OTR stimulation up-regulates OTR during labor. The OTR down-regulation seen after atosiban treatment adds to the direct relaxing effect of atosiban on the myometrium. In view of this, atosiban may prove to be a more useful tocolytic than the traditionally used beta2 agonists.

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Effect of Oxytocin Receptor and β2-Adrenoceptor Blockade on Myometrial Oxytocin Receptors in Parturient Rats1

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