Chung O, Unger T
Institute of Pharmacology, Christian-Albrechts-University Kiel, Germany.
Am J Hypertens. 1999 Dec;12(12 Pt 1-2):150S-156S. doi: 10.1016/s0895-7061(99)00218-6.
The renin-angiotensin system (RAS) is a widely studied hormonal system that comprises substrate-enzyme interactions, the end result of which is production of the active peptide angiotensin II (Ang II). Because Ang II affects blood pressure control, sodium and water homeostasis, and cardiovascular function and structure, a great deal of research effort has been directed toward blocking the RAS. Angiotensin II may also be involved in end-organ damage in hypertension, heart failure, and vascular disease. At least two subtypes of angiotensin II receptors have been identified: AT1 and AT2. The AT1 mediates all of the known actions of Ang II on blood pressure control. Additionally, research has indicated that the AT1 receptor modulates cardiac contractility and glomerular filtration, and increases renal tubular sodium reabsorption, and cardiac and vascular hypertrophy. Less is known regarding the function of the AT2 receptor. Evidence suggests that the AT2 receptor inhibits cell proliferation and reverses AT1-induced hypertrophy. Indeed, these receptors are thought to exert opposing effects. Angiotensin II AT1 receptor antagonists (AT1RA) inhibit the RAS at the receptor level by specifically blocking the AT1 receptor subtype. These drugs induce a dose-dependent blockade of Ang II effects, resulting in reduced blood pressure, urinary protein, and glomerular sclerosis. It is postulated that AT1RA may provide end-organ protection by blocking Ang II effects via the AT1 receptor, yet leaving the AT2 receptor unopposed. Consequently, these agents may reduce the morbidity and mortality that result from myocardial infarction (MI) and other conditions resulting from structural alterations in the heart, kidney, and vasculature.
肾素-血管紧张素系统（RAS）是一个被广泛研究的激素系统，它包括底物-酶相互作用，其最终结果是产生活性肽血管紧张素II（Ang II）。由于Ang II影响血压控制、钠和水平衡以及心血管功能和结构，大量的研究工作都致力于阻断RAS。血管紧张素II也可能参与高血压、心力衰竭和血管疾病中的终末器官损伤。至少已鉴定出两种血管紧张素II受体亚型：AT1和AT2。AT1介导了Ang II对血压控制的所有已知作用。此外，研究表明AT1受体调节心脏收缩力和肾小球滤过，并增加肾小管钠重吸收以及心脏和血管肥大。关于AT2受体的功能了解较少。有证据表明AT2受体抑制细胞增殖并逆转AT1诱导的肥大。事实上，这些受体被认为发挥相反的作用。血管紧张素II AT1受体拮抗剂（AT1RA）通过特异性阻断AT1受体亚型在受体水平抑制RAS。这些药物诱导对Ang II作用的剂量依赖性阻断，导致血压降低、尿蛋白减少和肾小球硬化。据推测，AT1RA可能通过阻断经由AT1受体的Ang II作用来提供终末器官保护，同时使AT2受体不受抑制。因此，这些药物可能降低心肌梗死（MI）以及由心脏、肾脏和血管结构改变引起的其他病症导致的发病率和死亡率。
