Raizada Veena, Skipper Betty, Luo Wentao, Griffith Jeffrey
Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131-0001, USA.
J Investig Med. 2007 Nov;55(7):341-59. doi: 10.2310/6650.2007.00020.
The renin-angiotensin system (RAS) is a hormonal system that controls body fluid volume, blood pressure, and cardiovascular function in both health and disease. Various tissues, including the heart and kidneys, possess individual locally regulated RASs. In each RAS, the substrate protein angiotensinogen is cleaved by the peptidases renin and angiotensin-converting enzyme to form the biologically active product angiotensin II, which acts as an intracrine cardiac and renal hormone. The components of each RAS, including aldosterone (ALDO), may be produced locally and/or may be delivered by or sequestered from the circulation. Overactivity of the cardiac RAS has been associated with cardiac diseases, including cardiac hypertrophy due to volume and/or pressure overload, heart failure, coronary artery disease with myocardial infarction, and hypertension. Overactivity of the renal RAS has been associated with various kidney diseases, including nephropathies and renal artery stenosis. The principal effects of an overactive RAS include the generation of reactive oxygen species, which leads to "oxidative stress," activation of the nuclear transcription factor kappaB, and stimulation of pathways and genes that promote vasoconstriction, endothelial dysfunction, cell hypertrophy, fibroblast proliferation, inflammation, excess extracellular matrix deposition, atherosclerosis, and thrombosis. It has been suggested that oxidative stress is the central mechanism underlying the pathogenesis of RAS-related and ALDO-related chronic cardiovascular and renal tissue injury and of cardiac arrhythmias and conduction disturbances.
肾素-血管紧张素系统（RAS）是一种激素系统，在健康和疾病状态下均能控制体液容量、血压及心血管功能。包括心脏和肾脏在内的各种组织都有各自局部调节的RAS。在每个RAS中，底物蛋白血管紧张素原被肽酶肾素和血管紧张素转换酶切割，形成生物活性产物血管紧张素II，它作为一种内分泌性心脏和肾脏激素发挥作用。每个RAS的组成成分，包括醛固酮（ALDO），可以在局部产生和/或可以从循环中递送或隔离。心脏RAS的过度激活与多种心脏疾病有关，包括因容量和/或压力过载导致的心肌肥厚、心力衰竭、伴有心肌梗死的冠状动脉疾病和高血压。肾脏RAS的过度激活与各种肾脏疾病有关，包括肾病和肾动脉狭窄。RAS过度活跃的主要影响包括活性氧的产生，这会导致“氧化应激”、核转录因子κB的激活，以及刺激促进血管收缩、内皮功能障碍、细胞肥大、成纤维细胞增殖、炎症、细胞外基质过度沉积、动脉粥样硬化和血栓形成的信号通路和基因。有人提出氧化应激是RAS相关和ALDO相关的慢性心血管和肾脏组织损伤以及心律失常和传导障碍发病机制的核心机制。
