Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary.
J Physiol Pharmacol. 2010 Oct;61(5):629-36.
The beneficial effects of pregnancy on the symptoms of inflammatory diseases are well documented. The modulation in the uterine functions in the presence of generalized inflammation, however, is much less characterized. The aim of the present study was to explore the modulatory action of adjuvant arthritis on the adrenergic functions of the uterus in nonpregnant and late pregnant rats. Adjuvant arthritis was induced by the subplantar injection of M. butyricum. Presynaptic functions were characterized by a superfusion technique and by registration of the contractions of isolated uterine rings elicited by electric field stimulation. The functions of the adrenoceptors were characterized by constructing concentration-response curves with agonists for both α- and β-receptors. Where these curves differed significantly from the control, the expressions of these receptors at the mRNA level were additionally determined. Adjuvant arthritis substantially decreased the uptake and release of [(3)H]noradrenaline in myometrial samples from nonpregnant rats, but caused no change at term. The electrically induced contractions were decreased by inflammation in both gestational states. Arthritis resulted in decreased β-adrenoceptor-mediated relaxation (in both the nonpregnant and the late-pregnant animals) and an increase in α-mediated contraction at term. It can be concluded that adjuvant arthritis deteriorates the adrenergic innervation of the uterus. The effects of exogenous sympathomimetics are shifted, favoring a state of higher contractility. If similar mechanisms are operative in humans, the present results could imply that β-adrenoceptor agonists are not ideal tocolytics when pregnancy is complicated by generalized inflammation.
妊娠对炎症性疾病症状的有益影响已有充分记录。然而,在全身性炎症存在的情况下,子宫功能的调节却知之甚少。本研究旨在探讨佐剂性关节炎对非妊娠和晚期妊娠大鼠子宫肾上腺素能功能的调节作用。佐剂性关节炎通过足底注射丁酸乳杆菌诱导。通过灌流技术和记录电场刺激引起的离体子宫环收缩来描述突触前功能。通过构建激动剂对 α-和 β-受体的浓度反应曲线来描述肾上腺素能受体的功能。如果这些曲线与对照有显著差异,则进一步确定这些受体在 mRNA 水平的表达。佐剂性关节炎显著降低了非妊娠大鼠子宫肌组织中 [(3)H]去甲肾上腺素的摄取和释放,但在足月时没有变化。在两种妊娠状态下,炎症都会导致电诱导收缩减少。关节炎导致在非妊娠和晚期妊娠动物中 β-肾上腺素能介导的松弛减少,而在足月时 α-介导的收缩增加。可以得出结论,佐剂性关节炎恶化了子宫的肾上腺素能神经支配。外源性拟交感神经药物的作用发生转移,有利于更高的收缩力状态。如果类似的机制在人类中起作用,那么本研究结果可能意味着,当妊娠伴有全身性炎症时,β-肾上腺素能激动剂不是理想的保胎药。