Liu Y J
Department of Analytical Pharmacology, King's College School of Medicine and Dentistry, Rayne Institute, London, UK.
Eur J Pharmacol. 1993 Aug 24;240(2-3):147-54. doi: 10.1016/0014-2999(93)90892-l.
Antagonist effect of losartan, a nonpeptide antagonist of angiotensin II, on angiotensin II induced contractile response was studied in five isolated smooth muscle assays. In the rabbit aorta and guinea-pig stomach assays, losartan competed with angiotensin II for the angiotensin receptors in an apparently simple manner, that is compliance with the basic criteria of Schild analysis for simple competition. Noncompliance, however, was observed in the guinea-pig ileum, rat ileum and guinea-pig trachea assays where losartan induced nonparallel rightward shifts of angiotensin II E/log[A] curves and the Schild plots were found to have slopes greater than unity. The observed deviations from simple competitive antagonism appeared to be different from those reported earlier, and a possible explanation involving tissue-dependent noncompetitive factor(s) is discussed.
在五项离体平滑肌试验中，研究了血管紧张素II的非肽拮抗剂氯沙坦对血管紧张素II诱导的收缩反应的拮抗作用。在兔主动脉和豚鼠胃试验中，氯沙坦以一种明显简单的方式与血管紧张素II竞争血管紧张素受体，即符合简单竞争的Schild分析的基本标准。然而，在豚鼠回肠、大鼠回肠和豚鼠气管试验中观察到不符合情况，在这些试验中，氯沙坦导致血管紧张素II的E/log[A]曲线向右非平行移动，并且发现Schild图的斜率大于1。观察到的与简单竞争性拮抗作用的偏差似乎与先前报道的不同，并且讨论了涉及组织依赖性非竞争性因素的可能解释。
