长期输注沙丁胺醇、地尔硫䓬和硝苯地平对去卵巢产后大鼠子宫收缩的影响。
The effects of long-term infusion of salbutamol, diltiazem and nifedipine on uterine contractions in the ovariectomized, post-partum rat.
作者信息
Abel M H, Hollingsworth M
出版信息
Br J Pharmacol. 1986 Jul;88(3):577-84. doi: 10.1111/j.1476-5381.1986.tb10238.x.
The sensitivity of the uterus to the inhibition of contractions by salbutamol, diltiazem or nifedipine was assessed in the ovariectomized, post-partum rat by dose-response curves following bolus intravenous (i.v.) administration. These tests were performed before (day 1), immediately after a 20 h i.v. infusion of salbutamol, diltiazem, nifedipine or appropriate control infusate (day 2) and after a further 20 h infusion of saline (day 3). In a further group of animals sensitivity to nifedipine was assessed before and after a 20 h infusion of salbutamol. Uterine contractions were monitored throughout infusions. Infusion of salbutamol (2 micrograms kg-1 min-1) produced an initial marked inhibition of uterine contractions, an effect which was not maintained despite continued infusion. Contractions reappeared after 2 h of infusion and reached pre-infusion levels by 5 h. The dose-response curve to salbutamol on day 2 was shifted more than 100 fold to the right compared with that on day 1. Sensitivity of the uterus on day 3 did not differ from that on day 1. Nifedipine (25 micrograms kg-1 min-1) produced sustained inhibition of uterine contractions throughout the 20 h of infusion. Sensitivity of the uterus to nifedipine could not, therefore, be tested on day 2; sensitivity on day 3 did not differ from that on day 1. In addition, there was no change in sensitivity of the uterus to nifedipine after a 20 h infusion of salbutamol. 4 Diltiazem (200 Ig kg-' min-') produced a marked initial inhibition of uterine contractions, with a partial return of contractions during continued infusion in 7 out of 12 animals so that mean integral values reached 40% of those pre-infusion. The dose-response curve to diltiazem on day 2 showed a 25 fold shift to the right compared with that on day 1 in 4 out of 12 animals where the test could be performed. Sensitivity of the uterus on day 3 did not differ from that on day 1. 5 These findings suggest that marked but reversible tolerance to the inhibitory actions of salbutamol on uterine contractions occurs during long-term infusion. There was no evidence of tolerance to the uterine actions of nifedipine, but there was evidence of tolerance to diltiazem in some animals.
通过大剂量静脉注射后绘制剂量反应曲线，评估去卵巢产后大鼠子宫对沙丁胺醇、地尔硫卓或硝苯地平抑制宫缩作用的敏感性。这些试验在给药前（第1天）、静脉输注沙丁胺醇、地尔硫卓、硝苯地平或相应对照输注液20小时后立即进行（第2天），以及再输注生理盐水20小时后进行（第3天）。在另一组动物中，评估在输注沙丁胺醇20小时前后子宫对硝苯地平的敏感性。在整个输注过程中监测子宫收缩情况。输注沙丁胺醇（2微克·千克⁻¹·分钟⁻¹）最初显著抑制子宫收缩，尽管持续输注，这种作用并未持续。输注2小时后宫缩重新出现，5小时后达到输注前水平。与第1天相比，第2天沙丁胺醇的剂量反应曲线右移超过100倍。第3天子宫的敏感性与第1天无差异。硝苯地平（25微克·千克⁻¹·分钟⁻¹）在整个20小时的输注过程中持续抑制子宫收缩。因此，第2天无法测试子宫对硝苯地平的敏感性；第3天的敏感性与第1天无差异。此外，输注沙丁胺醇20小时后子宫对硝苯地平的敏感性没有变化。地尔硫卓（200微克·千克⁻¹·分钟⁻¹）最初显著抑制子宫收缩，12只动物中有7只在持续输注过程中宫缩部分恢复，因此平均积分值达到输注前的40%。在12只可进行试验的动物中，有4只第2天地尔硫卓的剂量反应曲线与第1天相比右移25倍。第3天子宫的敏感性与第1天无差异。这些发现表明，长期输注期间，子宫对沙丁胺醇抑制宫缩作用产生显著但可逆的耐受性。没有证据表明子宫对硝苯地平的作用产生耐受性，但在一些动物中有证据表明对 地尔硫卓产生耐受性。
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