Dzau V J
Am J Cardiol. 1987 Jan 23;59(2):59A-65A. doi: 10.1016/0002-9149(87)90178-0.
The traditional concept of the renin-angiotensin system is a circulation-borne endocrine system whose components are secreted by different organs, i.e., renin from the kidney, angiotensinogen from the liver and angiotensin-converting enzyme from the lung. The product of the biochemical cascade, angiotensin II, acts on specific receptors on multiple target organs. Recent data, however, demonstrate that renin and angiotensin are synthesized locally in many tissues. The emerging concept--that angiotensin is produced locally at tissue sites by an endogenous renin-angiotensin system--has important implications to our understanding of cardiovascular homeostasis. This concept implies that local angiotensin concentrations may exceed those of plasma levels and may play an important role in the tonic control of vascular resistance, cardiac and adrenal functions as well as local intrarenal events. An important mechanism of action of converting enzyme inhibitors may be the blockade of tissue angiotensin generation. Hence, the tissue distribution and kinetics of converting enzyme inhibitors may be an important determinant of drug action. These findings have led us to speculate that aberrant tissue renin, angiotensinogen gene expression(s) or abnormalities in the regulation of the local renin-angiotensin system may result in such cardiovascular disorders as vasospasm, hypertension and cardiac hypertrophy.
肾素-血管紧张素系统的传统概念是一个通过血液循环的内分泌系统，其组成成分由不同器官分泌，即肾脏分泌肾素、肝脏分泌血管紧张素原、肺脏分泌血管紧张素转换酶。生化级联反应的产物血管紧张素II作用于多个靶器官上的特定受体。然而，最近的数据表明，肾素和血管紧张素在许多组织中是局部合成的。新出现的概念——血管紧张素由内源性肾素-血管紧张素系统在组织部位局部产生——对我们理解心血管稳态具有重要意义。这一概念意味着局部血管紧张素浓度可能超过血浆水平，并且可能在血管阻力、心脏和肾上腺功能以及肾内局部事件的紧张性控制中发挥重要作用。血管紧张素转换酶抑制剂的一个重要作用机制可能是阻断组织血管紧张素的生成。因此，血管紧张素转换酶抑制剂的组织分布和动力学可能是药物作用的一个重要决定因素。这些发现使我们推测，异常的组织肾素、血管紧张素原基因表达或局部肾素-血管紧张素系统调节异常可能导致血管痉挛、高血压和心脏肥大等心血管疾病。
