Roy B, Sicotte B, Brochu M, St-Louis J
Hôpital Ste-Justine, Department of Obstetrics and Gynecology, Faculty of Medicine, Université de Montréal, Québec, Canada.
Eur J Pharmacol. 1995 Jun 23;280(1):1-9. doi: 10.1016/0014-2999(95)00155-e.
The hypothesis that Ca2+ channel function is altered during pregnancy was tested by comparing responses to potassium chloride (KCl) and phenylephrine in aortic rings of virgin and term-pregnant rats under the influence of nifedipine and Bay K 8644. Maximum response to KCl was progressively reduced by increasing nifedipine concentrations (1.0-100 nM) in both groups of tissues. Nifedipine produced a smaller inhibition of KCl-induced contraction in aortic rings of pregnant than of virgin rats. It exerted little inhibition on the concentration-response curve to phenylephrine. The Ca2+ channel antagonist (100 nM) reduced the maximum response to the alpha-adrenoceptor agonist in rings from virgin rats, but had no effect in pregnant rats. Bay K 8644, a Ca2+ channel activator, potentiated the responses to low concentrations of both phenylephrine and KCl in the tissues of both virgin and pregnant rats, but did not affect maximum responses. It also induced concentration-dependent contractions in rings of virgin but not of pregnant rats. The effects of Bay K 8644 were markedly potentiated by precontracting the aorta with 10mM KCl. Nevertheless tissues from pregnant rats were still less responsive to Bay K 8644. However, when the strips were precontracted to the same level by different concentrations of KCl, the concentration-response curves to Bay K 8644 were identical in both groups. [3H]Nitrendipine binding to membrane preparations of the thoracic aorta was similar in virgin and pregnant rats.(ABSTRACT TRUNCATED AT 250 WORDS)
通过比较在硝苯地平和Bay K 8644作用下,未孕大鼠和足月妊娠大鼠主动脉环对氯化钾(KCl)和去氧肾上腺素的反应,来检验妊娠期间Ca2+通道功能发生改变这一假说。在两组组织中,随着硝苯地平浓度(1.0 - 100 nM)的增加,对KCl的最大反应逐渐降低。硝苯地平对妊娠大鼠主动脉环中KCl诱导的收缩的抑制作用小于未孕大鼠。它对去氧肾上腺素的浓度 - 反应曲线几乎没有抑制作用。Ca2+通道拮抗剂(100 nM)降低了未孕大鼠主动脉环对α - 肾上腺素能激动剂的最大反应,但对妊娠大鼠无影响。Ca2+通道激活剂Bay K 8644增强了未孕和妊娠大鼠组织对低浓度去氧肾上腺素和KCl的反应,但不影响最大反应。它还在未孕大鼠的主动脉环中诱导了浓度依赖性收缩,但在妊娠大鼠中未诱导。用10 mM KCl预收缩主动脉可显著增强Bay K 8644的作用。然而,妊娠大鼠的组织对Bay K 8644的反应仍然较低。但是,当用不同浓度的KCl将条带预收缩到相同水平时,两组对Bay K 8644的浓度 - 反应曲线是相同的。[3H]尼群地平与胸主动脉膜制剂的结合在未孕和妊娠大鼠中相似。(摘要截短至250字)