title: Effects of experimentally induced diabetes mellitus on pharmacologically and electrically elicited myometrial contractility.
abstract: 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 α- and β-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 α1B-adrenoceptors in non-pregnant rats from 14.65 to 18.39 μg/mL (P < 0.05), whereas the expression of α1D-adrenoceptors decreased (from 42.87 to 35.67 μg/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.
authors.affiliation: Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Spiegl
authors.forename: István
authors.initials: I
authors.lastname: Zupkó
authors.forename: Renáta
authors.initials: R
authors.lastname: Minorics
authors.forename: Gábor
authors.initials: G
authors.lastname: Csík
authors.forename: Dénes
authors.initials: D
authors.lastname: Csonka
authors.forename: George
authors.initials: G
authors.lastname: Falkay
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology; D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D016640:Diabetes, Gestational / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D005865:Gestational Age; D009126:Muscle Relaxation / Q000187:drug effects; D009215:Myometrium / Q000187:drug effects* / Q000294:innervation* / Q000378:metabolism / Q000503:physiopathology; D009638:Norepinephrine / Q000494:pharmacology; D010120:Oxytocics / Q000494:pharmacology*; D010121:Oxytocin / Q000494:pharmacology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018045:Receptors, Oxytocin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013311:Streptozocin; D013726:Terbutaline / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects*
chemical_list: C547715:Adra1a protein, rat; C547718:Adra1b protein, rat; C547721:Adra1d protein, rat; D058646:Adrenergic alpha-1 Receptor Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D010120:Oxytocics; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D018343:Receptors, Adrenergic, beta-2; D018045:Receptors, Oxytocin; D010121:Oxytocin; D013311:Streptozocin; D013726:Terbutaline; D009638:Norepinephrine