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多巴酚丁胺的α-肾上腺素能受体激动剂活性对麻醉猫变力性选择性的重要性。

The importance of the alpha-adrenoceptor agonist activity of dobutamine to inotropic selectivity in the anaesthetized cat.

作者信息

Kenakin T P, Johnson S F

出版信息

Eur J Pharmacol. 1985 May 20;111(3):347-54. doi: 10.1016/0014-2999(85)90641-7.

Abstract

Doses of dobutamine (steady-state infusions) required to increase inotropy (as measured by isovolumic indices of contractility) were lower than those required to produce tachycardia in the anaesthetized cat. When compared to isoprenaline, dobutamine produced less tachycardia for common increases in inotropy and thus demonstrated inotropic selectivity in this model. Dobutamine also produced mild pressor effects which were potentiated by beta-adrenoceptor blockade with propranolol. In efforts to define the role of the partial agonist activity of dobutamine for alpha-adrenoceptors in the production of selective inotropy the effects of dobutamine infusions were observed in cats pretreated with the alpha-adrenoceptor antagonist phentolamine. In phentolamine-treated cats dobutamine did not demonstrate inotropic selectivity and showed a relationship between increased inotropy and tachycardia which was not significantly different from that obtained with isoprenaline. In contrast, phentolamine did not change the relationship between isoprenaline-induced tachycardia and increased inotropy. These data suggest that the agonist activity of dobutamine for alpha-adrenoceptors could be responsible for selective inotropy in the anaesthetized cat probably by baroreceptor-mediated reflex modulation of heart rate and/or possible stimulation of inotropic cardiac alpha-adrenoceptors.

摘要

增加心肌收缩力(以等容收缩性指标衡量)所需的多巴酚丁胺剂量(稳态输注)低于麻醉猫产生心动过速所需的剂量。与异丙肾上腺素相比,多巴酚丁胺在常见的心肌收缩力增加时引起的心动过速较少,因此在该模型中表现出心肌收缩力选择性。多巴酚丁胺还产生轻度升压作用,普萘洛尔的β肾上腺素受体阻滞可增强这种作用。为了确定多巴酚丁胺对α肾上腺素受体的部分激动剂活性在产生选择性心肌收缩力中的作用,观察了用α肾上腺素受体拮抗剂酚妥拉明预处理的猫输注多巴酚丁胺的效果。在酚妥拉明处理的猫中,多巴酚丁胺未表现出心肌收缩力选择性,并且显示出心肌收缩力增加与心动过速之间的关系,这与用异丙肾上腺素获得的关系无显著差异。相比之下,酚妥拉明并未改变异丙肾上腺素引起的心动过速与心肌收缩力增加之间的关系。这些数据表明,多巴酚丁胺对α肾上腺素受体的激动剂活性可能是麻醉猫产生选择性心肌收缩力的原因,可能是通过压力感受器介导的心率反射调节和/或可能刺激心肌α肾上腺素受体。

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