Angiotensin II receptor subtypes: selective antagonists and functional correlates.
Angiotensin II receptor subtypes: selective antagonists and functional correlates.
复制标题
血管紧张素 II 受体亚型：选择性拮抗剂和功能相关物。
作者：
P. Timmermans;R. D. Smith
血管紧张素II（Ang II）受体异质性目前由新的亚型选择性药物氯沙坦（AT1）和PD123177（AT2）定义。虽然这两种亚型已被克隆和测序，只有AT1受体已被证明具有重要的生理或病理生理作用。AT1和AT2受体在正常和衰竭的心脏组织中都有发现。它们存在于肌细胞、内皮细胞、成纤维细胞、冠状动脉平滑肌细胞和外周交感神经上。AT1受体介导了Ang II在心肌细胞中的几乎所有作用，即使心脏组织可能含有超过50%的AT2位点。在内皮细胞中，功能反应主要是AT 1。在成纤维细胞中，初步数据表明，AT2受体可能参与胶原合成。在离体组织中，Ang II在心房组织中具有有限的正性肌力作用，但在心室组织中不具有正性肌力作用，该作用可被氯沙坦阻断。血管紧张素II也可能对冠状动脉阻力有滋补作用，因为血管紧张素抑制剂可以增加冠状动脉流量。ACE（Ang II合成）抑制剂和Ang II受体拮抗剂在心力衰竭的实验模型中产生有益作用，表明Ang II是心力衰竭的重要介质。由于ACE抑制剂也增强缓激肽，并且是Ang II合成的非特异性抑制剂（Ang II对两种受体亚型的可用性），因此可以预期存在一些差异。然而，目前，缓激肽的有益作用是有争议的，心脏和其他组织中的主要功能性Ang II受体是AT 1亚型。（250字处删节）
Angiotensin II (Ang II) receptor heterogeneity is currently defined by the new subtype-selective agents, losartan (AT1) and PD123177 (AT2). Although both subtypes have been cloned and sequenced, only the AT1 receptor has been shown to have an important physiological or pathophysiological role. AT1 and AT2 receptors are found in both normal and failing cardiac tissue. They are found on myocytes, endothelial cells, fibroblasts, coronary arterial smooth muscle cells, and peripheral sympathetic nerves. The AT1 receptors mediate virtually all of the effects of Ang II in myocytes even though cardiac tissue may contain over 50% AT2 sites. In endothelial cells, functional responses are predominately AT1. In fibroblasts, preliminary data suggest that AT2 receptors may be involved in collagen synthesis. In isolated tissue, Ang II has a limited positive inotropic effect in atrial, but not in ventricular tissue, which is blocked by losartan. Ang II may also have a tonic effect on coronary artery resistance as angiotensin inhibitors can increase coronary flow. Both ACE (Ang II synthesis) inhibitors and Ang II receptor antagonists produce beneficial effects in experimental models of heart failure, suggesting Ang II is an important mediator of heart failure. Because ACE inhibitors also potentiate bradykinin and are non-specific inhibitors of Ang II synthesis (availability of Ang II to both receptor subtypes) some differences can be anticipated. At the present time, however, the beneficial role of bradykinin is controversial and the predominant functional Ang II receptor in the heart and other tissues is the AT1 subtype.(ABSTRACT TRUNCATED AT 250 WORDS)