Department of Morphology, Biological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.
Department of Physiology & Biophysics - Biological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.
Curr Neuropharmacol. 2022;20(6):1212-1228. doi: 10.2174/1570159X19666210719142300.
Along with other canonical systems, the renin-angiotensin system (RAS) has shown important roles in stress. This system is a complex regulatory proteolytic cascade composed of various enzymes, peptides, and receptors. Besides the classical (ACE/Ang II/AT1 receptor) and the counter-regulatory (ACE2/Ang-(1-7)/Mas receptor) RAS axes, evidence indicates that nonclassical components, including Ang III, Ang IV, AT and AT, can also be involved in stress.
This comprehensive review summarizes the current knowledge on the participation of RAS components in different adverse environmental stimuli stressors, including air jet stress, cage switch stress, restraint stress, chronic unpredictable stress, neonatal isolation stress, and post-traumatic stress disorder.
In general, activation of the classical RAS axis potentiates stress-related cardiovascular, endocrine, and behavioral responses, while the stimulation of the counter-regulatory axis attenuates these effects. Pharmacological modulation in both axes is optimistic, offering promising perspectives for stress-related disorders treatment. In this regard, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are potential candidates already available since they block the classical axis, activate the counter-regulatory axis, and are safe and efficient drugs.
与其他经典系统一样，肾素-血管紧张素系统（RAS）在应激中表现出重要作用。该系统是由各种酶、肽和受体组成的复杂调节蛋白水解级联。除了经典（ACE/Ang II/AT1 受体）和代偿性（ACE2/Ang-（1-7）/Mas 受体）RAS 轴外，有证据表明，非经典成分，包括 Ang III、Ang IV、AT 和 AT，也可能参与应激。
本综述总结了 RAS 成分参与不同环境刺激应激源的最新知识，包括空气射流应激、笼切换应激、束缚应激、慢性不可预测应激、新生隔离应激和创伤后应激障碍。
一般来说，经典 RAS 轴的激活增强了与应激相关的心血管、内分泌和行为反应，而代偿性轴的刺激则减弱了这些效应。对这两个轴的药理学调节是乐观的，为应激相关疾病的治疗提供了有希望的前景。在这方面，血管紧张素转换酶抑制剂和血管紧张素受体阻滞剂是潜在的候选药物，因为它们阻断经典轴，激活代偿性轴，并且是安全有效的药物。
