EFFECTS OF EXPERIMENTALLY INDUCED DIABETES MELLITUS ON PHARMACOLOGICALLY AND ELECTRICALLY ELICITED MYOMETRIAL CONTRACTILITY

摘要

1. Diabetes is one of the most frequent complications of gestation, affecting approximately 7% of pregnancies. However, little is known about its effects on electrically and pharmacologically stimulated myometrial contractility. The aim of the present study was to investigate the consequences of streptozotocin (STZ)-induced diabetes on: (i) electrical field stimulation (EFS)-evoked contraction of isolated uterine rings as a function of gestational age; and (ii) the uterotonic and tocolytic actions of alpha- and beta-adrenoceptor stimulation, respectively. The effects of oxytocin in late pregnancy were also investigated.2. During pregnancy, EFS-evoked contractions of isolated uterine rings from intact rats declined, whereas isolated uterine rings from diabetic rats exhibited continuously low sensitivity to EFS.3. In non-pregnant rats, diabetes resulted in increased noradrenaline-mediated contractility and a decreased relaxation response to terbutaline. At the mRNA level, diabetes enhanced the expression of alpha_(1B)-adrenoceptors in non-pregnant rats from 14.65 to 18.39 mug/mL (P < 0.05), whereas the expression of alpha_(1D)-adrenoceptors decreased (from 42.87 to 35.67 mug/mL; P < 0.05). During pregnancy, the responses to these sympathomimetics did not differ between diabetic and intact rats.4. In late pregnancy (on Days 15 and 21), oxytocin caused greater maximum contractility of uterine rings from diabetic rats without affecting the EC_(50). In addition, on Day 15 of pregnancy, the expression of oxytocin receptors in the myometrium of diabetic rats was higher than that in intact rats.5. The results of the present study indicate that experimental diabetes facilitates gestation-induced denervation and increases myometrial sensitivity to oxytocin in late pregnancy. If similar mechanisms operate in humans, this could contribute to a tendency to premature uterine contractions in diabetes-complicated pregnancies.