肾素 - 血管紧张素 - 醛固酮系统阻滞的研究进展

肾素-血管紧张素-醛固酮系统起初被认为是较简单的神经体液调节机制之一。但是,这一想法随着RAAS阻滞剂:肾素阻滞剂、血管紧张素转换酶抑制剂(ACEI)、AT1受体拮抗剂及盐皮质激素受体拮抗剂的深入研究而受到挑战。因此,RAAS的组成、以上药物发挥作用的具体通路及副作用均得到重新定义。在RAAS阻滞剂的应用过程中,机体肾素水平升高,并刺激肾素原受体(即无活性的肾素前体,PRR),进而对机体造成不良影响。同理,在AT1受体拮抗剂的应用过程中,血浆血管紧张素II的水平升高,并与2型血管紧张素II(AT2)受体结合,进而对机体产生有利作用。此外,随着ACEI及ARB的应用,血管紧张素1-7水平升高,其与Mas受体结合,发挥心脏及肾脏保护的作用,还可通过刺激干细胞发挥组织修复作用。

Key Developments in Renin-Angiotensin-Aldosterone System Inhibition

The renin-angiotensin-aldosterone system (RAAS) was initially thought to be fairly simple. However, this idea has been challenged following the development of RAAS blockers, including renin inhibitors, angiotensin-converting-enzyme (ACE) inhibitors, type 1 angiotensin II (AT1 )-receptor blockers and mineralocorticoid-receptor antagonists. Consequently, new RAAS components and pathways that might contribute to the effectiveness of these drugs and/or their adverse effects have been identified. An increase in renin levels during RAAS blockade might result in harmful effects via stimulation of the prorenin receptor (PRR, the inactive precursor of rennin). The increase in angiotensin II levels that occurs during AT1 -receptor blockade might result in beneficial effects via stimulation of type 2 angiotensin II (AT2) receptors. Moreover, angiotensin 1 -7 levels increase during ACE inhibition and AT1-receptor blockade, resulting in Mas receptor activation and the induction of cardioprotective and renoprotective effects, including stimulation of tissue repair by stem cells.