Nonclassical renin-angiotensin system and renal function.
Nonclassical renin-angiotensin system and renal function.
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DOI：
10.1002/cphy.c120002
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发表时间：
2012-10
影响因子：
5.8
通讯作者：
Chappell MC
中科院分区：
文献类型：
--
作者：
Chappell MC
肾素-血管紧张素系统（RAS）是通过肾脏和非肾脏机制对血压进行生理调节的最重要的激素系统之一。事实上，RAS的失调被认为是心血管病理学发展的主要因素，包括肾损伤，通过抑制血管紧张素转化酶（ACE）或通过选择性拮抗剂阻断血管紧张素1型受体（AT 1 R）来阻断该系统构成了有效的治疗方案。现在，随着肾脏和其他组织内RAS的多种组分的鉴定，该系统实际上由不同的血管紧张素肽组成，这些血管紧张素肽具有由不同的受体亚型介导的不同生物学作用。经典RAS可定义为ACE-Ang II AT 1 R轴，其促进血管收缩、水摄入、钠潴留和其他机制以维持血压，以及增加病理条件下的氧化应激、纤维化、细胞生长和炎症。相反，主要由AngII/AngIII-AT 2 R通路和ACE 2-Ang-（1-7）-AT 7 R轴组成的非经典RAS通常通过增加一氧化氮和胰高血糖素来对抗受刺激的AngII-AT 1 R轴的作用，并介导血管舒张、尿钠排泄、利尿和减少氧化应激。此外，越来越多的证据表明，这些非经典RAS组分有助于经典系统的治疗性阻断，以降低血压和减弱各种肾损伤指标，以及有助于正常的肾功能。
The renin-angiotensin-system (RAS) constitutes one of the most important hormonal systems in the physiological regulation of blood pressure through renal and non-renal mechanisms. Indeed, dysregulation of the RAS is considered a major factor in the development of cardiovascular pathologies including kidney injury and blockade of this system by the inhibition of angiotensin converting enzyme (ACE) or blockade of the angiotensin type 1 receptor (AT1R) by selective antagonists constitutes an effective therapeutic regimen. It is now apparent with the identification of multiple components of the RAS within the kidney and other tissues that the system is actually composed of different angiotensin peptides with diverse biological actions mediated by distinct receptor subtypes. The classic RAS can be defined as the ACE-Ang II AT1R axis that promotes vasoconstriction, water intake, sodium retention and other mechanisms to maintain blood pressure, as well as increase oxidative stress, fibrosis, cellular growth and inflammation in pathological conditions. In contrast, the non-classical RAS composed primarily of the AngII/Ang III–AT2R pathway and the ACE2-Ang-(1-7)-AT7R axis generally opposes the actions of a stimulated Ang II-AT1R axis through an increase in nitric oxide and prostaglandins and mediates vasodilation, natriuresis, diuresis, and a reduced oxidative stress. Moreover, increasing evidence suggests that these non-classical RAS components contribute to the therapeutic blockade of the classical system to reduce blood pressure and attenuate various indices of renal injury, as well as contribute to normal renal function.
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