Moore G J, Ko E M
Pharmacology. 1980;20(1):36-41. doi: 10.1159/000137342.
The effects of several paired analogs of angiotensin II and angiotensin III, designed as antagonists, have been compared in isolated smooth muscle (rat uterus) and by in vivo rat blood pressure assay. These analogs were (1) the angiotensin II series: (1-sarcosine, 7-X, 8-isoleucine-) angiotensin II, and (2) the angiotensin III series: (1-despartyl, 7-X, 8-isoleucine)angiotensin II, where X=sarcosine, N-methyl-L-alanine or DL-nipecotic acid. All of these analogs had very low pressor and myotropic activities in the vagotomized, ganglion-blocked rat and the isolated rat uterus, respectively, although the angiotensin II analogs had significantly higher intrinsic pressor activity than the angiotensin III analogs. In addition, the angiotensin II analogs were potent antagonists of the contractile response to angiotensin II in the rat uterus whereas the angiotensin III analogs were weak inhibitors. These observations demonstrate the existence of functional differences for the proline residue in angiotensin II and angiotensin III analogs and may reflect differences in conformation and modes of binding to smooth muscle receptors between the two classes of peptides.
作为拮抗剂设计的几种血管紧张素II和血管紧张素III的配对类似物，其作用已在离体平滑肌（大鼠子宫）和通过体内大鼠血压测定法进行了比较。这些类似物为：(1)血管紧张素II系列：(1-肌氨酸，7-X，8-异亮氨酸-)血管紧张素II，以及(2)血管紧张素III系列：(1-去天门冬氨酰，7-X，8-异亮氨酸)血管紧张素II，其中X =肌氨酸、N-甲基-L-丙氨酸或DL-哌啶酸。所有这些类似物在迷走神经切断、神经节阻断的大鼠和离体大鼠子宫中分别具有非常低的升压和致肌活性，尽管血管紧张素II类似物的内在升压活性明显高于血管紧张素III类似物。此外，血管紧张素II类似物是大鼠子宫中对血管紧张素II收缩反应的有效拮抗剂，而血管紧张素III类似物是弱抑制剂。这些观察结果证明了血管紧张素II和血管紧张素III类似物中脯氨酸残基存在功能差异，并且可能反映了这两类肽在构象和与平滑肌受体结合方式上的差异。
