Kobori Hiroyuki, Navar L Gabriel
Departments of Medicine and Physiology, and Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, USA.
Int Rev Thromb. 2011;6(2):108-116.
An activated intrarenal reninangiotensin system (RAS) plays a crucial role in the pathogenesis of hypertension and chronic kidney diseases (CKD). Angiotensinogen (AGT) is the only known substrate for renin, which is the rate-limiting enzyme of the RAS. Because the levels of AGT are close to the Michaelis-Menten constant for renin, AGT levels can also control the RAS activity, and upregulation of AGT may lead to elevated angiotensin peptide levels and increases in blood pressure. Recent studies on experimental animal models have documented the involvement of AGT in the intrarenal RAS activation and development of hypertension. Enhanced intrarenal AGT mRNA and/or protein levels occur in experimental models of hypertension and kidney diseases supporting important roles in the development and progression of hypertension and kidney diseases. Urinary excretion rates of AGT provide a specific index of intrarenal RAS status in angiotensin II-infused rats. Also, a direct quantitative method was recently developed to measure urinary AGT using human AGT ELISA. These data prompted us to measure urinary AGT in patients with hypertension and CKD, and investigate correlations with clinical parameters. This brief review will address the potential of urinary AGT as a novel biomarker of the intrarenal RAS status in hypertension and CKD.
激活的肾内肾素 - 血管紧张素系统（RAS）在高血压和慢性肾脏病（CKD）的发病机制中起关键作用。血管紧张素原（AGT）是肾素唯一已知的底物，而肾素是RAS的限速酶。由于AGT水平接近肾素的米氏常数，AGT水平也可控制RAS活性，AGT上调可能导致血管紧张素肽水平升高和血压升高。最近对实验动物模型的研究证明AGT参与肾内RAS激活和高血压的发展。在高血压和肾脏疾病的实验模型中，肾内AGT mRNA和/或蛋白质水平增强，这支持了其在高血压和肾脏疾病发生发展中的重要作用。在输注血管紧张素II的大鼠中，AGT的尿排泄率提供了肾内RAS状态的一个特定指标。此外，最近开发了一种使用人AGT ELISA直接定量测量尿AGT的方法。这些数据促使我们测量高血压和CKD患者的尿AGT，并研究其与临床参数的相关性。这篇简短的综述将探讨尿AGT作为高血压和CKD中肾内RAS状态新型生物标志物的潜力。
