scholarly journals Mitochondria-produced superoxide mediates angiotensin II-induced inhibition of neuronal potassium current

2010 ◽  
Vol 298 (4) ◽  
pp. C857-C865 ◽  
Author(s):  
Jing-Xiang Yin ◽  
Rui-Fang Yang ◽  
Shumin Li ◽  
Alex O. Renshaw ◽  
Yu-Long Li ◽  
...  
Keyword(s):  
Potassium Current ◽  
Biological Significance ◽  
Primary Source ◽  
Oxygen Species ◽  
Ang Ii ◽  
Patch Clamp Technique ◽  
Voltage Gated ◽  
Calmodulin Kinase ◽  
The Central Nervous System ◽  
Stimulation Of

Reactive oxygen species (ROS), particularly superoxide (O2·−), have been identified as key signaling intermediates in ANG II-induced neuronal activation and sympathoexcitation associated with cardiovascular diseases, such as hypertension and heart failure. Studies of the central nervous system have identified NADPH oxidase as a primary source of O2·− in ANG II-stimulated neurons; however, additional sources of O2·−, including mitochondria, have been mostly overlooked. Here, we tested the hypothesis that ANG II increases mitochondria-produced O2·− in neurons and that increased scavenging of mitochondria-produced O2·− attenuates ANG II-dependent intraneuronal signaling. Stimulation of catecholaminergic (CATH.a) neurons with ANG II (100 nM) increased mitochondria-localized O2·− levels, as measured by MitoSOX Red fluorescence. This response was significantly attenuated in neurons overexpressing the mitochondria-targeted O2·−-scavenging enzyme Mn-SOD. To examine the biological significance of the ANG II-mediated increase in mitochondria-produced O2·−, we used the whole cell configuration of the patch-clamp technique to record the well-characterized ANG II-induced inhibition of voltage-gated K+ current ( IKv) in neurons. Adenovirus-mediated Mn-SOD overexpression or pretreatment with the cell-permeable antioxidant tempol (1 mM) significantly attenuated ANG II-induced inhibition of IKv. In contrast, pretreatment with extracellular SOD protein (400 U/ml) had no effect. Mn-SOD overexpression also inhibited ANG II-induced activation of Ca2+/calmodulin kinase II, a redox-sensitive protein known to modulate IKv. These data indicate that ANG II increases mitochondrial O2·−, which mediates, at least in part, ANG II-induced activation of Ca2+/calmodulin kinase II and inhibition of IKv in neurons.

Reactive Oxygen Species-Mediated Homologous Downregulation of Angiotensin II Type 1 Receptor Mrna by Angiotensin II

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 688-688
Author(s):  
Toshihiro Ichiki ◽  
Kotaro Takeda ◽  
Akira Takeshita
Keyword(s):  
Reactive Oxygen Species ◽  
Angiotensin Ii ◽  
Nadph Oxidase ◽  
Mrna Expression ◽  
Crucial Role ◽  
Oxygen Species ◽  
Ang Ii ◽  
Stimulation Of

58 Recent studies suggest a crucial role of reactive oxygen species (ROS) for the signaling of Angiotensin II (Ang II) through type 1 Ang II receptor (AT1-R). However, the role of ROS in the regulation of AT1-R expression has not been explored. In this study, we examined the effect of an antioxidant on the homologous downregulation of AT1-R by Ang II. Ang II (10 -6 mol/L) decreased AT1-R mRNA with a peak suppression at 6 hours of stimulation in rat aortic vascular smooth muscle cells (VSMC). Ang II dose-dependently (10 -8 -10 -6 ) suppressed AT1-R mRNA at 6 hours of stimulation. Preincubation of VSMC with N-acetylcysteine (NAC), a potent antioxidant, almost completely inhibited the Ang II-induced downregulation of AT1-R mRNA. The effect of NAC was due to stabilization of the AT1-R mRNA that was destabilized by Ang II. Ang II did not affect the promoter activity of AT1-R gene. Diphenylene iodonium (DPI), an inhibitor of NADH/NADPH oxidase failed to inhibit the Ang II-induced AT1-R mRNA downregulation. The Ang II-induced AT1-R mRNA downregulation was also blocked by PD98059, an extracellular signal-regulated protein kinase (ERK) kinase inhibitor. Ang II-induced ERK activation was inhibited by NAC as well as PD98059 whereas DPI did not inhibit it. To confirm the role of ROS in the regulation of AT1-R mRNA expression, VSMC were stimulated with H 2 O 2 . H 2 O 2 suppressed the AT1-R mRNA expression and activated ERK. These results suggest that production of ROS and activation of ERK are critical for downregulation of AT1-R mRNA. The differential effect of NAC and DPI on the downregulation of AT1-R mRNA may suggest the presence of other sources than NADH/NADPH oxidase pathway for ROS in Ang II signaling. Generation of ROS through stimulation of AT1-R not only mediates signaling of Ang II but may play a crucial role in the adaptation process of AT1-R to the sustained stimulation of Ang II.

Erythropoietin in COVID-19-Induced Neuroinflammation; EPO Plus Losartan Might be Promising

2020 ◽  
Author(s):  
Reza Nejat ◽  
Ahmad Shahir Sadr ◽  
David Najafi
Keyword(s):  
Inflammatory Mediators ◽  
Renin Angiotensin System ◽  
Oxygen Species ◽  
Ang Ii ◽  
Angiotensin System ◽  
Intracellular Messengers ◽  
The Central Nervous System ◽  
Harmful Effects

Introduction: Neuroinflammation is the inflammatory reaction in the central nervous system (CNS) provoked by diverse insults. This phenomenon results in a cascade of release of inflammatory mediators and intracellular messengers such as reactive oxygen species. The elicited responses are the cause of many neurological and neurodegenerative disorders. Erythropoietin (EPO) has been considered effective in attenuating this inflammatory process in the CNS, yet its administration in COVID-19 needs meticulously designed studies. Discussion: Neuroinflammation in COVID-19 due to probable contribution of renin-angiotensin system dysregulation resulting in surplus of Ang II and owing to the synergistic interaction between this octapeptide and EPO needs special consideration. Both of these compounds increase intracellular Ca2+ which may induce release of cytokine and inflammatory mediators leading to aggravation of neuroinflammation. In addition, Ang II elevates HIF even in normoxia which by itself increases EPO. It is implicated that EPO and HIF may likely increase in patients with COVID-19 which makes administration of EPO to these patients hazardous. Furthermore, papain-like protease of SARS-CoV2 as a deubiquitinase may also increase HIF. Conclusion: It is hypothesized that administration of EPO to patients with COVID-19-induced neuroinflammation may not be safe and in case EPO is needed for any reason in this disease adding of losartan may block AT1R-mediated post-receptor harmful effects of Ang II in synergism with EPO. Inhibition of papain-like protease might additionally decrease HIF in this disease. More in vitro, in vivo and clinical studies are needed to validate these hypotheses.

scholarly journals Eag1 K+Channel: Endogenous Regulation and Functions in Nervous System

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Bo Han ◽  
Tursonjan Tokay ◽  
Guangming Zhang ◽  
Peng Sun ◽  
Shangwei Hou
Keyword(s):  
Nervous System ◽  
Recent Progress ◽  
Neurological Diseases ◽  
Tumor Development ◽  
K Channel ◽  
Oxygen Species ◽  
Voltage Gated ◽  
Channel Regulation ◽  
The Central Nervous System

Ether-à-go-go1 (Eag1, Kv10.1, KCNH1) K+channel is a member of the voltage-gated K+channel family mainly distributed in the central nervous system and cancer cells. Like other types of voltage-gated K+channels, the EAG1 channels are regulated by a variety of endogenous signals including reactive oxygen species, rendering the EAG1 to be in the redox-regulated ion channel family. The role of EAG1 channels in tumor development and its therapeutic significance have been well established. Meanwhile, the importance of hEAG1 channels in the nervous system is now increasingly appreciated. The present review will focus on the recent progress on the channel regulation by endogenous signals and the potential functions of EAG1 channels in normal neuronal signaling as well as neurological diseases.

scholarly journals Voltage-gated divalent currents in descending vasa recta pericytes

2010 ◽  
Vol 299 (4) ◽  
pp. F862-F871 ◽  
Author(s):  
Zhong Zhang ◽  
Hai Lin ◽  
Chunhua Cao ◽  
Sandeep Khurana ◽  
Thomas L. Pallone
Keyword(s):  
Charge Carrier ◽  
Charge Carriers ◽  
Slow Inactivation ◽  
Ang Ii ◽  
Patch Clamp Technique ◽  
Voltage Gated ◽  
Vasa Recta ◽  
Maximal Activation ◽  
Voltage Dependent ◽  
Glomerular Arterioles

Multiple voltage-gated Ca2+ channel (CaV) subtypes have been reported to participate in control of the juxtamedullary glomerular arterioles of the kidney. Using the patch-clamp technique, we examined whole cell CaV currents of pericytes that contract descending vasa recta (DVR). The dihydropyridine CaV agonist FPL64176 (FPL) stimulated inward Ca2+ and Ba2+ currents that activated with threshold depolarizations to −40 mV and maximized between −20 and −10 mV. These currents were blocked by nifedipine (1 μM) and Ni2+ (100 and 1,000 μM), exhibited slow inactivation, and conducted Ba2+ > Ca2+ at a ratio of 2.3:1, consistent with “long-lasting” L-type CaV. In FPL, with 1 mM Ca2+ as charge carrier, Boltzmann fits yielded half-maximal activation potential ( V1/2) and slope factors of −57.9 mV and 11.0 for inactivation and −33.3 mV and 4.4 for activation. In the absence of FPL stimulation, higher concentrations of divalent charge carriers were needed to measure basal currents. In 10 mM Ba2+, pericyte CaV currents activated with threshold depolarizations to −30 mV, were blocked by nifedipine, exhibited voltage-dependent block by diltiazem (10 μM), and conducted Ba2+ > Ca2+ at a ratio of ∼2:1. In Ca2+, Boltzmann fits to the data yielded V1/2 and slope factors of −39.6 mV and 10.0 for inactivation and 2.8 mV and 7.7 for activation. In Ba2+, V1/2 and slope factors were −29.2 mV and 9.2 for inactivation and −5.6 mV and 6.1 for activation. Neither calciseptine (10 nM), mibefradil (1 μM), nor ω-agatoxin IVA (20 and 100 nM) blocked basal Ba2+ currents. Calciseptine (10 nM) and mibefradil (1 μM) also failed to reverse ANG II-induced DVR vasoconstriction, although raising mibefradil concentration to 10 μM was partially effective. We conclude that DVR pericytes predominantly express voltage-gated divalent currents that are carried by L-type channels.

Regulation of Ca2+-activated K+ channels by multifunctional Ca2+/calmodulin-dependent protein kinase

2000 ◽  
Vol 279 (2) ◽  
pp. F283-F288 ◽  
Author(s):  
Steven C. Sansom ◽  
Rong Ma ◽  
Pamela K. Carmines ◽  
David A. Hall
Keyword(s):  
Mesangial Cells ◽  
Specific Inhibitor ◽  
Ang Ii ◽  
Voltage Gated ◽  
Regulatory Enzymes ◽  
Calmodulin Kinase ◽  
Intracellular Ca ◽  
Dependent Protein ◽  
Voltage Gated Channels ◽  
Inside Out

Activation of mesangial cells by ANG II provokes release of intracellular Ca2+ stores and subsequent Ca2+influx through voltage-gated channels, events that are reflected by a large transient increase in intracellular concentration [Ca2+]i followed by a modest sustained elevation in [Ca2+]i. These ANG II-induced alterations in [Ca2+]i elicit activation of large Ca2+-activated K+ channels (BKCa) in a negative-feedback manner. The mechanism of this BKCa feedback response may involve the direct effect of intracellular Ca2+ on the channel and/or channel activation by regulatory enzymes. The present study utilized patch-clamp and fura 2 fluorescence techniques to assess the involvement of multifunctional calcium calmodulin kinase II (CAMKII) in the BKCa feedback response. In cell-attached patches, KN62 (specific inhibitor of CAMKII) either abolished or reduced to near zero the ANG II-induced BKCa feedback response. This phenomenon did not reflect direct effects of KN62 on the BKCa channel, because this agent alone did not significantly alter BKCa channel activity in inside-out patches. KN62 also failed to alter either the transient peak or sustained plateau phases of the [Ca2+]i response to ANG II. In inside-out patches (1 μM Ca2+ in bath), calmodulin plus ATP activated BKCa channels in the presence but not the absence of CAMKII. These observations are consistent with the postulate that CAMKII is involved in the BKCa feedback response of mesangial cells, acting to potentiate the influence of increased [Ca2+]i on the BKCa channel or a closely associated regulator of the channel. An additional effect of CAMKII to activate a voltage-gated Ca2+ channel cannot be ruled out by these experiments.

Angiotensin II, reactive oxygen species, and Ca2+ signaling in afferent arterioles

2005 ◽  
Vol 289 (5) ◽  
pp. F1012-F1019 ◽  
Author(s):  
Susan K. Fellner ◽  
William J. Arendshorst
Keyword(s):  
Calcium Release ◽  
Rat Kidney ◽  
Specific Inhibitor ◽  
Oxygen Species ◽  
Ang Ii ◽  
Inositol Trisphosphate Receptor ◽  
Afferent Arterioles ◽  
Trisphosphate Receptor ◽  
Calcium Induced Calcium Release ◽  
Stimulation Of

In afferent arteriolar vascular smooth muscle cells, ANG II induces a rise in cytosolic Ca2+ ([Ca2+]i) via inositol trisphosphate receptor (IP3R) stimulation and by activation of the adenine diphosphate ribose (ADPR) cyclase to form cyclic ADPR, which sensitizes the ryanodine receptor (RyR) to Ca2+. We hypothesize that ANG II stimulation of NAD(P)H oxidases leads to the formation of superoxide anion (O2−·), which, in turn, activates ADPR cyclase. Afferent arterioles were isolated from rat kidney with the magnetized microsphere and sieving technique and loaded with fura-2 to measure [Ca2+]i. ANG II rapidly increased [Ca2+]i by 124 ± 12 nM. In the presence of apocynin, a specific inhibitor of NAD(P)H oxidase assembly, the [Ca2+]i response was reduced to 35 ± 5 nM ( P < 0.01). Tempol, a superoxide dismutase mimetic, did not alter the [Ca2+]i response to ANG II at a concentration of 10−4 M (99 ± 12 nM), but 10−3 M tempol reduced the response to 32 ± 3 nM ( P < 0.01). The addition of nicotinamide, an inhibitor of ADPR cyclase, to apocynin or tempol (10−3 M) resulted in no further inhibition. Measurement of superoxide production with the fluorescent probe tempo 9-AC showed that ANG II caused an increase of 48 ± 20 arbitrary units; apocynin or diphenyl iodonium (an inhibitor of flavoprotein oxidases) inhibited the response by 94%. Hydrogen peroxide (H2O2) was studied at physiological (10−7 M) and higher concentrations. In the presence of H2O2 (10−7 M), neither baseline [Ca2+]i nor the response to ANG II was altered (125 ± 15 nM), whereas H2O2 (10−6 and 10−5 M) inhibited the [Ca2+]i response to ANG II by 35 and 46%, respectively. We conclude that ANG II rapidly activates NAD(P)H oxidases of afferent arterioles, leading to the formation of O2−·, which then stimulates ADPR cyclase to form cADPR. cADPR, by sensitizing the RyR to Ca2+, augments the Ca2+ response (calcium-induced calcium release) initiated by activation of the IP3R.

scholarly journals Endogenous reactive oxygen species modulates voltage-gated sodium channels in dorsal root ganglia of rats

2011 ◽  
Vol 110 (5) ◽  
pp. 1439-1447 ◽  
Author(s):  
Han-Jun Wang ◽  
Yu-Long Li ◽  
Li-Bin Zhang ◽  
Irving H. Zucker ◽  
Lie Gao ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Pressor Response ◽  
Reactive Oxygen ◽  
Muscle Afferents ◽  
Transient Receptor Potential Vanilloid ◽  
Oxygen Species ◽  
Patch Clamp Technique ◽  
Voltage Gated

We recently reported that reactive oxygen species (ROS) plays an excitatory role in modulation of the exercise pressor reflex (EPR) in normal rats. In this study, we further tested two independent hypotheses: 1) ROS interacts with EPR-related ionotropic receptors such as the purinergic receptors (P2) and transient receptor potential vanilloid 1 receptors (TRPV1) to indirectly modulate the EPR function; 2) ROS directly affects excitability of muscle afferents by modulating the voltage-gated sodium (Nav) channels. To test the first hypothesis, we performed animal experiments to investigate the effect of the SOD mimetic 4-hydroxy-2,2,6,6-tetramethyl piperidine 1-oxyl (Tempol) on the pressor response to hindlimb intra-arterial (IA) injection of either α,β-methylene ATP (a P2X agonist) or capsaicin (a TRPV1 agonist) in decerebrate rats. To test the second hypothesis, we used the patch-clamp technique to determine the effect of ROS on Nav channels on the soma of muscle afferents. We also performed local microinjection of a sodium channel blocker, tetrodotoxin (TTX), into ipsilateral L4/L5 dorsal root ganglia (DRGs) to investigate whether the blockade of Nav channels by TTX affects the EPR function. We found that Tempol did not affect the pressor response to injection of either capsaicin or α,β-methylene ATP but significantly decreased the Nav current in small and medium-sized 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI)-labeled DRG neurons. A membrane-permeant superoxide dismutase, polyethylene glycol (PEG)-SOD, had an effect on the Nav current in these neurons similar to that of Tempol. Microinjection of TTX into L4/L5 DRGs dramatically attenuated the pressor response to static contraction induced by electrical stimulation of L4/L5 ventral roots. These data suggest that ROS modulates the EPR by affecting the activity of the Nav channels on muscle afferents.

scholarly journals Copper-Containing Alloy as Immunoregulatory Material in Bone Regeneration via Mitochondrial Oxidative Stress

2021 ◽  
Vol 8 ◽  
Author(s):  
Daorong Xu ◽  
Jikun Qian ◽  
Xin Guan ◽  
Ling Ren ◽  
Kaifan Yang ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Repair ◽  
Primary Source ◽  
Oxygen Species ◽  
Group 14 ◽  
Mitochondrial Oxidative Stress ◽  
Factor Type ◽  
Stimulation Of

In the mammalian skeletal system, osteogenesis and angiogenesis are closely linked by type H vessels during bone regeneration and repair. Our previous studies confirmed the promotion of these processes by copper-containing metal (CCM) in vitro and in vivo. However, whether and how the coupling of angiogenesis and osteogenesis participates in the promotion of bone regeneration by CCM in vivo is unknown. In this study, M2a macrophages but not M2c macrophages were shown to be immunoregulated by CCM. A CCM, 316L−5Cu, was applied to drilling hole injuries of the tibia of C57/6 mice for comparison. We observed advanced formation of cortical bone and type H vessels beneath the new bone in the 316L−5Cu group 14 and 21 days postinjury. Moreover, the recruitment of CD206-positive M2a macrophages, which are regarded as the primary source of platelet-derived growth factor type BB (PDGF-BB), was significantly promoted at the injury site at days 14 and 21. Under the stimulation of CCM, mitochondria-derived reactive oxygen species were also found to be upregulated in CD206hi M2a macrophages in vitro, and this upregulation was correlated with the expression of PDGF-BB. In conclusion, our results indicate that CCM promotes the evolution of callus through the generation of type H vessels during the process of bone repair by upregulating the expression of PDGF-BB derived from M2a macrophages.

Angiotensin II stimulation of VEGF mRNA translation requires production of reactive oxygen species

2006 ◽  
Vol 290 (4) ◽  
pp. F927-F936 ◽  
Author(s):  
Denis Feliers ◽  
Yves Gorin ◽  
Goutam Ghosh-Choudhury ◽  
Hanna E. Abboud ◽  
Balakuntalam S. Kasinath
Keyword(s):  
Reactive Oxygen Species ◽  
Respiratory Chain ◽  
Mrna Translation ◽  
Mitochondrial Respiratory Chain ◽  
Ros Production ◽  
Oxygen Species ◽  
Ang Ii ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
Stimulation Of

ANG II, a mediator of renal injury in diabetic renal disease, promotes vascular endothelial growth factor (VEGF) mRNA translation in proximal tubular epithelial (MCT) cells (Feliers D, Duraisamy S, Barnes JL, Ghosh-Choudhury G, and Kasimath BS. Am J Physiol Renal Physiol 288: F521–F529, 2005). The mechanism by which ANG II elicits this effect is not known. ANG II is known to induce oxidative stress and the rapidity of the effect suggested a role for reactive oxygen species (ROS). The aim of this study is to test the hypothesis that ANG II regulates VEGF mRNA translation in MCT cells through ROS production. In MCT cells exposed to 1 nM ANG II, ROS production was increased in a time-dependent manner. Inhibition of ROS production by N-acetylcysteine (NAC), a precursor of glutathione, and diphenyleneiodonium (DPI), an inhibitor of flavoproteins that include NAD(P)H oxidase, prevented ANG II-stimulated VEGF protein expression. NAC and DPI also inhibited phosphorylation of 4E-BP1 on Thr46 and association of eIF4E with eIF4G, steps that are important in the initiation phase of mRNA translation. NAC and DPI also blocked Akt activation which is required for 4E-BP1 phosphorylation. LY-294002, a selective phosphatidylinositol (PI 3-kinase) inhibitor, did not prevent ROS accumulation in response to ANG II, whereas DPI blocked ANG II activation of PI 3-kinase, demonstrating that ROS production is upstream of the PI 3-kinase signaling pathway. Preincubation with catalase abolished ANG II stimulation of VEGF expression and mRNA translation, suggesting involvement of hydrogen peroxide (H2O2). H2O2 reproduced the effects of ANG II on VEGF expression and aforementioned parameters of mRNA translation. Finally, neither preincubation of MCT cells with specific inhibitors of the mitochondrial respiratory chain nor inactivation of the mitochondrial respiratory chain in MCT cells prevented ANG II stimulation of VEGF expression. Inhibition of nitric oxide synthase by l-NAME had no effect on ANG II stimulation of VEGF expression. These data show that ROS, generated probably through activation of an NAD(P)H oxidase, mediate ANG II stimulation of VEGF mRNA translation.

RAS in the Central Nervous System: Potential Role in Neuropsychiatric Disorders

2018 ◽  
Vol 25 (28) ◽  
pp. 3333-3352 ◽  
Author(s):  
Natalia Pessoa Rocha ◽  
Ana Cristina Simoes e Silva ◽  
Thiago Ruiz Rodrigues Prestes ◽  
Victor Feracin ◽  
Caroline Amaral Machado ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Neuropsychiatric Disorders ◽  
Extensive Literature ◽  
Ang Ii ◽  
Mas Receptor ◽  
The Central Nervous System ◽  
The Brain

Background: The Renin-Angiotensin System (RAS) is a key regulator of cardiovascular and renal homeostasis, but also plays important roles in mediating physiological functions in the central nervous system (CNS). The effects of the RAS were classically described as mediated by angiotensin (Ang) II via angiotensin type 1 (AT1) receptors. However, another arm of the RAS formed by the angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and the Mas receptor has been a matter of investigation due to its important physiological roles, usually counterbalancing the classical effects exerted by Ang II. Objective: We aim to provide an overview of effects elicited by the RAS, especially Ang-(1-7), in the brain. We also aim to discuss the therapeutic potential for neuropsychiatric disorders for the modulation of RAS. Method: We carried out an extensive literature search in PubMed central. Results: Within the brain, Ang-(1-7) contributes to the regulation of blood pressure by acting at regions that control cardiovascular functions. In contrast with Ang II, Ang-(1-7) improves baroreflex sensitivity and plays an inhibitory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts effects related to blood pressure regulation, but also acts as a neuroprotective component of the RAS, for instance, by reducing cerebral infarct size, inflammation, oxidative stress and neuronal apoptosis. Conclusion: Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic and hemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding the ACE2/Ang-(1-7)/Mas receptor axis in human CNS.

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