肾素-血管紧张素系统(RAS)是公认的最古老,最重要的动脉血压调节剂之一,心血管,和肾功能。RAS研究最近出现了新的领域,远远超出了其作为有效血管收缩剂的经典范式,醛固酮释放刺激剂,或者钠保留激素.首先,已经发现了RAS的两个新成员,其中包括肾素/(Pro)肾素受体(PRR)和血管紧张素转换酶2(ACE2)。最近的研究表明,肾素原可能独立于经典的ACE/ANGII/AT1受体轴作用于PRR,而ACE2可能降解ANGII产生ANG(1-7),激活Mas受体.第二,越来越多的证据表明ANGII可能作为细胞内肽激活细胞内和/或核受体。第三,目前,关于系统性RAS与肾内RAS对血压生理调节和高血压发展的相对贡献存在争议。本文的目的是回顾和讨论从最近的研究中获得的新见解和观点,这些研究使用过表达或缺乏一种关键酶的新型转基因小鼠,ANG肽,或RAS的受体。这些信息可能有助于我们更好地理解ANGII的行为,无论是独立还是通过与系统其他成员的互动,在健康和疾病中调节肾功能和血压。
The renin-angiotensin system (RAS) is well-recognized as one of the oldest and most important regulators of arterial blood pressure, cardiovascular, and renal function. New frontiers have recently emerged in the RAS research well beyond its classic paradigm as a potent vasoconstrictor, an aldosterone release stimulator, or a sodium-retaining hormone. First, two new members of the RAS have been uncovered, which include the renin/(Pro)renin receptor (PRR) and angiotensin-converting enzyme 2 (ACE2). Recent studies suggest that prorenin may act on the PRR independent of the classical ACE/ANG II/AT1 receptor axis, whereas ACE2 may degrade ANG II to generate ANG (1-7), which activates the Mas receptor. Second, there is increasing evidence that ANG II may function as an intracellular peptide to activate intracellular and/or nuclear receptors. Third, currently there is a debate on the relative contribution of systemic versus intrarenal RAS to the physiological regulation of blood pressure and the development of hypertension. The objectives of this article are to
review and discuss the new insights and perspectives derived from recent studies using novel transgenic mice that either overexpress or are deficient of one key enzyme, ANG peptide, or receptor of the RAS. This information may help us better understand how ANG II acts, both independently or through interactions with other members of the system, to regulate the kidney function and blood pressure in health and disease.