PDF(Pubmed)
Abstract：
Recent years have seen a resurgence of interest for the renin-angiotensin-aldosterone system in critically ill patients. Emerging data suggest that this vital homeostatic system, which plays a crucial role in maintaining systemic and renal hemodynamics during stressful conditions, is altered in septic shock, ultimately leading to impaired angiotensin II-angiotensin II type 1 receptor signaling. Indeed, available evidence from both experimental models and human studies indicates that alterations in the renin-angiotensin-aldosterone system during septic shock can occur at three distinct levels: 1. Impaired generation of angiotensin II, possibly attributable to defects in angiotensin-converting enzyme activity; 2. Enhanced degradation of angiotensin II by peptidases; and/or 3. Unavailability of angiotensin II type 1 receptor due to internalization or reduced synthesis. These alterations can occur either independently or in combination, ultimately leading to an uncoupling between the renin-angiotensin-aldosterone system input and downstream angiotensin II type 1 receptor signaling. It remains unclear whether exogenous angiotensin II infusion can adequately address all these mechanisms, and additional interventions may be required. These observations open a new avenue of research and offer the potential for novel therapeutic strategies to improve patient prognosis. In the near future, a deeper understanding of renin-angiotensin-aldosterone system alterations in septic shock should help to decipher patients\' phenotypes and to implement targeted interventions.
摘要：
近年来，危重病人对肾素-血管紧张素-醛固酮系统的兴趣重新兴起。新出现的数据表明，这个至关重要的稳态系统，在压力条件下对维持全身和肾脏血流动力学起着至关重要的作用，在感染性休克时发生了改变，最终导致血管紧张素II-血管紧张素II1型受体信号传导受损。的确,来自实验模型和人体研究的现有证据表明,感染性休克期间肾素-血管紧张素-醛固酮系统的改变可发生在三个不同的水平:1.血管紧张素II的生成受损，可能归因于血管紧张素转换酶活性的缺陷;2.肽酶对血管紧张素II的降解增强;和/或3.由于内在化或合成减少导致血管紧张素II1型受体的不可用性。这些改变可以独立发生或组合发生，最终导致肾素-血管紧张素-醛固酮系统输入和下游血管紧张素II1型受体信号之间的解偶联。目前尚不清楚外源性血管紧张素II输注是否可以充分解决所有这些机制。可能需要额外的干预措施。这些观察为研究开辟了新的途径，并为改善患者预后的新治疗策略提供了潜力。在不久的将来,对感染性休克中肾素-血管紧张素-醛固酮系统改变的更深入了解应有助于破译患者的表型并实施有针对性的干预措施.
