Dennedy Michael C, Houlihan Diarmaid D, McMillan Helen, Morrison John J
Department of Obstetrics and Gynaecology, Clinical Sciences Institute, National University of Ireland Galway, University College Hospital.
Am J Obstet Gynecol. 2002 Sep;187(3):641-7. doi: 10.1067/mob.2002.125277.
The purpose of this study was to investigate the functional selectivity of the beta(3)-adrenoreceptor agonist BRL 37344 and the beta(2)-adrenoreceptor agonist ritodrine for their putative receptors in human pregnant myometrium in vitro and to examine the possibility that BRL 37344 may exert an effect on other beta-adrenoreceptor subtypes. This study also aimed comparatively to evaluate the in vitro effects of BRL 37344 and ritodrine on human vascular tissue tone.
The effects of BRL 37344 (1 nmol/L-100 micromol/L) and ritodrine (1 nmol/L-100 micromol/L) on isometric tension recordings that were performed in isolated myometrial strips that were obtained at elective cesarean delivery and in human umbilical artery rings that were obtained at term were measured. Antagonism of the effects of BRL 37344 and ritodrine in human myometrial tissue was investigated with the antagonists butoxamine (1 micromol/L), propranolol (1 micromol/L), and bupranolol (1 micromol/L). The concentrations that produced a 50% maximal effect, the mean maximal inhibition that was achieved, and the percentage of contractility that was observed were compared.
Bupranolol (n = 6), but not butoxamine (n = 6) or propranolol (n = 6), antagonized the relaxant effects of BRL 37344 in human pregnant myometrium; all three compounds (n = 6, respectively) antagonized the effects of ritodrine. At concentrations of >1 micromol/L, ritodrine exerted a significantly more potent vasodilatory effect than BRL 37344 on human umbilical artery tone (P <.01).
The relaxant effects of BRL 37344 appear to be mediated solely through the beta(3)-adrenoreceptor agonist, although ritodrine may exert an effect on beta(1)-, beta(2)-, and beta(3)-adrenoreceptor agonists. This and the reduction in vascular tissue effects observed with BRL 37344 suggest that uterine beta(3)-adrenoreceptor modulation may provide a novel scientific approach to tocolysis with fewer vascular adverse effects.
本研究旨在调查β₃肾上腺素能受体激动剂BRL 37344和β₂肾上腺素能受体激动剂利托君在体外人妊娠子宫肌层中对其假定受体的功能选择性，并研究BRL 37344对其他β肾上腺素能受体亚型产生作用的可能性。本研究还旨在比较评估BRL 37344和利托君对人体血管组织张力的体外作用。
测量了BRL 37344（1纳摩尔/升 - 100微摩尔/升）和利托君（1纳摩尔/升 - 100微摩尔/升）对在择期剖宫产时获取的离体子宫肌条以及足月时获取的人脐动脉环上进行的等长张力记录的影响。用拮抗剂布托沙明（1微摩尔/升）、普萘洛尔（1微摩尔/升）和布普洛尔（1微摩尔/升）研究了BRL 37344和利托君在人子宫肌层组织中的拮抗作用。比较了产生50%最大效应的浓度、达到的平均最大抑制以及观察到的收缩力百分比。
布普洛尔（n = 6）而非布托沙明（n = 6）或普萘洛尔（n = 6）拮抗了BRL 37344对人妊娠子宫肌层的舒张作用；所有三种化合物（分别为n = 6）均拮抗了利托君的作用。在浓度>1微摩尔/升时，利托君对人脐动脉张力的血管舒张作用比BRL 37344显著更强（P <.01）。
BRL 37344的舒张作用似乎仅通过β₃肾上腺素能受体激动剂介导，尽管利托君可能对β₁ - 、β₂ - 和β₃ - 肾上腺素能受体激动剂产生作用。这一点以及观察到的BRL 37344对血管组织作用的减弱表明，子宫β₃肾上腺素能受体调节可能为宫缩抑制提供一种新的科学方法，且血管不良反应较少。
