Resch Béla Endre, Ducza Eszter, Gáspár Róbert, Falkay George
Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary.
Mol Reprod Dev. 2003 Oct;66(2):166-71. doi: 10.1002/mrd.10337.
The use of beta2-Adrenergic Receptor (AR) agonists and the potential use of alpha1-AR blockers as tocolytics raise the question of how they influence placental circulation. The receptor profile was characterized via the amounts of the mRNA of alpha1-AR subtypes and beta2-ARs. The mRNAs were detected by reverse transcription-polymerase chain reaction. Electric field stimulation (EFS) was applied to test the pharmacological reactivity of the placental vessels. Expressions of beta2- and all subtypes of alpha1-AR mRNA were demonstrated in human placental vessels, and were significantly higher in the arteries. A significant difference was not found between the veins and the arteries as concerns the amount of alpha1D-AR mRNA. There was a preponderance of alpha1A- and alpha1B-AR mRNA as compared to alpha1D-AR mRNA both in the arteries and in the veins. beta2-AR agonists and alpha1-AR antagonists antagonized the EFS-induced contractions of the placental arteries in a dose-dependent manner. These effects were significantly less marked on veins at all applied doses. Urapidil antagonized the EFS-induced contractions of both the placental arterial and vein rings in a dose-dependent manner. The beta2-, alpha1A-, and alpha1B-AR are the important subtypes involved in the regulation of the contractility of the human term placental vessels. The possible increase in placental blood flow mediated by these ARs can even be beneficial during pregnancy. Accordingly, the use of beta2-AR agonists and the potential use of alpha1-blockers as tocolytics seem safe on the basis of in vitro examinations as concerns the placental circulation.
β2肾上腺素能受体(AR)激动剂的使用以及α1-AR阻滞剂作为宫缩抑制剂的潜在用途引发了它们如何影响胎盘循环的问题。通过α1-AR亚型和β2-AR的mRNA量来表征受体谱。通过逆转录-聚合酶链反应检测mRNA。应用电场刺激(EFS)来测试胎盘血管的药理反应性。在人胎盘血管中证实了β2-AR和α1-AR所有亚型的mRNA表达,且在动脉中显著更高。就α1D-AR mRNA量而言,静脉和动脉之间未发现显著差异。与α1D-AR mRNA相比,无论是在动脉还是静脉中,α1A-和α1B-AR mRNA都占优势。β2-AR激动剂和α1-AR拮抗剂以剂量依赖性方式拮抗EFS诱导的胎盘动脉收缩。在所有应用剂量下,这些作用在静脉上均明显不那么显著。乌拉地尔以剂量依赖性方式拮抗EFS诱导的胎盘动脉和静脉环收缩。β2-、α1A-和α1B-AR是参与调节足月人胎盘血管收缩性的重要亚型。这些AR介导的胎盘血流可能增加在孕期甚至可能是有益的。因此,基于体外检查,就胎盘循环而言,使用β2-AR激动剂和α1-阻滞剂作为宫缩抑制剂似乎是安全的。