Sandberg K, Ji H
Department of Medicine, Georgetown University Medical Center, Washington, DC, USA.
Semin Nephrol. 2000 Sep;20(5):402-16.
A considerable amount of data have implicated angiotensin receptors (AT receptors) in the development and maintenance of essential hypertension and renovascular hypertension as well as in progressive renal pathologies. Inhibition of angiotensin II (Ang II) action by blocking Ang II formation through angiotensin-converting enzyme (ACE) inhibitors, or by blocking AT1 receptors directly using subtype-selective nonpeptide antagonists, has been found to attenuate the proteinuria, microalbuminuria, glomerulosclerosis, and nephrosclerosis in a variety of experimental models and in clinical trials. This review will first broadly discuss AT receptor subtypes in terms of their structure, function, tissue distribution and signaling. Secondly, the mechanistic differences between ACE inhibition and AT1 receptor blockade will be examined because these pharmaceutical agents are widely used tools to investigate the role of AT receptors in renal disease. Lastly, experimental models of essential hypertension, renovascular hypertension and progressive renal disease will be presented, which include the Fawn-hooded rat, the stroke prone spontaneously hypertensive rat, renal mass ablation and the 2K1C and 1K1C animal models. The overall goal of this review is to critically evaluate the data regarding the role of AT receptors in the pathophysiology of renal disease.
大量数据表明，血管紧张素受体（AT受体）在原发性高血压和肾血管性高血压的发生及维持过程中，以及在进行性肾脏病变中均发挥着作用。通过血管紧张素转换酶（ACE）抑制剂阻断血管紧张素II（Ang II）的形成，或使用亚型选择性非肽拮抗剂直接阻断AT1受体，从而抑制Ang II的作用，已发现在多种实验模型和临床试验中，这可减轻蛋白尿、微量白蛋白尿、肾小球硬化和肾硬化。本综述将首先广泛讨论AT受体亚型的结构、功能、组织分布和信号传导。其次，将研究ACE抑制和AT1受体阻断之间的机制差异，因为这些药物是广泛用于研究AT受体在肾脏疾病中作用的工具。最后，将介绍原发性高血压、肾血管性高血压和进行性肾脏疾病的实验模型，其中包括淡色肥胖大鼠、易中风自发性高血压大鼠、肾大部切除以及二肾一夹（2K1C）和一肾一夹（1K1C）动物模型。本综述的总体目标是批判性地评估有关AT受体在肾脏疾病病理生理学中作用的数据。
