: Along with other canonical systems, the renin-angiotensin system (RAS) has shown essential roles in stress. This system is a complex regulatory proteolytic cascade composed of various enzymes, peptides, and receptors. Besides the classical (ACE/Ang II/AT 1 receptor) and the counter-regulatory (ACE2/Ang-(1-7)/Mas receptor) RAS axes, evidence indicates that non-classical components, including Ang III, Ang IV, AT 2, and AT 4, can also be involved in stress. Objective and methods: 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. Results and conclusion: In general, activating 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 because they block the classical axis, activate the counter-regulatory axis, and are safe and efficient drugs.
Objectives: To evaluate the impact of genetic deletion of receptors of the counterregulatory arms of the renin-angiotensin system in depressive-like behaviors. Methods: 8-12 weeks-old male mice wild-type (WT, C57BL/6J) and mice with genetic deletion of MrgD (MrgD KO) or Mas receptors (Mas KO) were subjected to the Forced Swim Test (FST) and the Tail Suspension Test (TST). Brain-derived neurotrophic factor (BDNF) levels were measured by enzyme-linked immunosorbent assay (ELISA). Blockade of Mas was performed by acute intracerebroventricular (icv) injection of its selective antagonist, A779. Results: No statistical difference in immobility time was observed between MrgD KO and WT male animals subjected to FST and TST. However, acute icv injection of A779 significantly increased the immobility time of MrgD KO male mice subjected to FST and TST, suggesting the involvement of Mas in preventing depression-like behavior. Indeed, Mas KO male animals showed increased immobility time in FST and TST, evidencing a depressive-like behavior in these animals, in addition to a reduction in BDNF levels in the prefrontal cortex and hippocampus. No changes in BDNF levels were observed in MrgD KO male animals. Conclusion: Our data showed that Mas plays an important role in the neurobiology of depression probably by modulating BDNF expression. On the contrary, lack of MrgD did not alter depressive-like behavior, which was supported by the lack of alterations in BDNF levels.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.