Caritis S N, Chiao J P, Moore J J, Ward S M
Department of Obstetrics and Gynecology, University of Pittsburgh School of Medicine, Magee-Womens Hospital, Pennsylvania 15123.
Am J Physiol. 1987 Oct;253(4 Pt 1):E410-7. doi: 10.1152/ajpendo.1987.253.4.E410.
We have developed a model in pregnant sheep to investigate pharmacological agents used for suppression of preterm labor. This model allows repetitive determinations of uterine contractility and simultaneous measurements of myometrial receptor and postreceptor events. We used the model to study the beta-adrenergic agent ritodrine. We infused 11 pregnant sheep with ritodrine and 3 with physiological saline for 24 h. Oxytocin boluses were given before and at 5 and 22 h after onset of the infusion. Myometrial biopsies were obtained before and immediately after the infusion. After 22 h of ritodrine infusion, uterine contractility in response to the same oxytocin bolus was 50% greater than at 5 h (P less than 0.02). Myometrial membrane beta-adrenergic receptor density decreased 49% (P less than 0.005), and catecholamine-stimulated adenylate cyclase activity was reduced 70% (P less than 0.005). The model thus demonstrates that use of the beta-adrenergic agonist ritodrine in a clinically relevant manner results in tachyphylaxis of its effects on both physiological parameters and the receptor cascade system.
我们在怀孕绵羊身上建立了一个模型，以研究用于抑制早产的药物制剂。该模型能够重复测定子宫收缩力，并同时测量子宫肌层受体及受体后事件。我们使用该模型研究了β-肾上腺素能药物利托君。我们给11只怀孕绵羊输注利托君，给3只输注生理盐水，持续24小时。在输注开始前、输注开始后5小时和22小时给予催产素推注。在输注前和输注后立即获取子宫肌层活检样本。在输注利托君22小时后，对相同催产素推注的子宫收缩反应比5小时时增强了50%（P<0.02）。子宫肌层膜β-肾上腺素能受体密度降低了49%（P<0.005），儿茶酚胺刺激的腺苷酸环化酶活性降低了70%（P<0.005）。因此，该模型表明，以临床相关方式使用β-肾上腺素能激动剂利托君会导致其对生理参数和受体级联系统的作用出现快速耐受性。
