Kramkowski K, Mogielnicki A, Buczko W
Department of Pharmacodynamics, Medical University of Białystok, Białystok, Poland.
J Physiol Pharmacol. 2006 Dec;57(4):529-39.
Although the use of angiotensin converting enzyme inhibitors (ACE-Is) in clinical practice brought the great chance to recognize the RAS role in the physiology and pathology, there are still many questions which we cannot answer. This article reviews actually known pathways of angiotensin II (Ang II) and other peptides of renin-angiotensin system (RAS) production and their physiological significance. The various carboxy- and aminopeptidases generate a range of peptides, like Ang II, Ang III, Ang IV, Ang-(1-7) and Ang-(1-9) possessing their own and known biological activity. In this issue especially the alternative pathways of Ang II synthesis involving enzymes other than angiotensin-converting enzyme (ACE) are discussed. We present many evidences for the significance of a new pathway of Ang II production. It has been clearly shown that Ang I may be converted to Ang-(1-9) by angiotensin-converting enzyme-related carboxypeptidase (ACE-2) and then into Ang II in some tissues, but the enzymes responsible for this process are unknown till now. Although there are many data proving the existence of alternative pathways of Ang II production, we can still block only ACE and angiotensin receptor 1 (AT(1)) in clinical practice. It seems that a lot needs to be done before we can wildly complexively control RAS and treat more effectively cardiovascular disorders such as hypertension or heart failure.
尽管在临床实践中使用血管紧张素转换酶抑制剂（ACE-Is）为认识肾素-血管紧张素系统（RAS）在生理和病理过程中的作用带来了重大契机，但仍有许多问题我们无法解答。本文综述了目前已知的血管紧张素II（Ang II）及肾素-血管紧张素系统其他肽类的生成途径及其生理意义。多种羧肽酶和氨肽酶可产生一系列具有自身已知生物活性的肽类，如Ang II、Ang III、Ang IV、Ang-(1-7)和Ang-(1-9)。在本期中，特别讨论了涉及血管紧张素转换酶（ACE）以外的酶的Ang II合成的替代途径。我们提供了许多证据证明Ang II生成新途径的重要性。已经清楚表明，在某些组织中，血管紧张素I可被血管紧张素转换酶相关羧肽酶（ACE-2）转化为Ang-(1-9)，然后再转化为Ang II，但至今负责此过程的酶仍不清楚。尽管有许多数据证明存在Ang II生成的替代途径，但在临床实践中我们目前仍只能阻断ACE和血管紧张素受体1（AT(1)）。在我们能够全面复杂地控制RAS并更有效地治疗诸如高血压或心力衰竭等心血管疾病之前，似乎还有很多工作要做。
