Higher Angiotensin II type 1 receptor (AT1R) levels and activity in the post-mortem brains of older persons with Alzheimer's disease

2021 ◽  
Author(s):  
Caglar Cosarderelioglu ◽  
Lolita S Nidadavolu ◽  
Claudene J George ◽  
Ruth Marx ◽  
Laura Powell ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Amyloid Β ◽  
Renin Angiotensin System ◽  
Angiotensin Receptors ◽  
Post Mortem ◽  
Protein Levels ◽  
Normal Individuals ◽  
Markers Of Oxidative Stress

Abstract Aging is a key risk factor in Alzheimer's dementia (AD) development and progression. The primary dementia-protective benefits of Angiotensin II subtype 1 receptor (AT1R) blockers are believed to arise from systemic effects on blood pressure. However, a brain-specific renin-angiotensin system (b-RAS) exists, which can be altered by AT1R blockers. Brain RAS acts mainly through three angiotensin receptors: AT1R, AT2R, and AT4R. Changes in these brain angiotensin receptors may accelerate the progression of AD. Using post-mortem frontal cortex brain samples of age- and sex-matched cognitively normal individuals (n = 30) and AD patients (n = 30), we sought to dissect the b-RAS changes associated with AD and assess how these changes correlate with brain markers of oxidative stress, inflammation, and mitochondrial dysfunction as well as amyloid-β and paired helical filament tau pathologies. Our results show higher protein levels of the pro-inflammatory AT1R and phospho-ERK (pERK) in the brains of AD participants. Brain AT1R levels and pERK correlated with higher oxidative stress, lower cognitive performance, and higher tangle and amyloid-β scores. This study identifies molecular changes in b-RAS and offers insight into the role of b-RAS in AD-related brain pathology.

Inhibition of chymase protects against diabetes-induced oxidative stress and renal dysfunction in hamsters

2010 ◽  
Vol 299 (6) ◽  
pp. F1328-F1338 ◽  
Author(s):  
Yasutaka Maeda ◽  
Toyoshi Inoguchi ◽  
Ryoko Takei ◽  
Fumi Sawada ◽  
Shuji Sasaki ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Angiotensin Ii ◽  
Renal Dysfunction ◽  
Transforming Growth Factor ◽  
Renin Angiotensin System ◽  
Transforming Growth Factor Β ◽  
Pathophysiological Role ◽  
Chymase Inhibitor

Accumulating evidence suggests that the intrarenal renin-angiotensin system may be involved in the progression of diabetic nephropathy. Chymase is a potent local angiotensin II-forming enzyme in several species, including humans and hamsters. However, the pathophysiological role of chymase is not fully understood. Here, we report a causal role of chymase in diabetic nephropathy and the therapeutic effectiveness of chymase inhibition. In the present study, renal chymase expression was markedly upregulated in streptozotocin-induced diabetic hamsters. Oral administration of a specific chymase inhibitor, TEI-F00806, completely ameliorated proteinuria, the overexpression of transforming growth factor-β and fibronectin in glomeruli, and renal mesangial expansion, by normalizing the increase in intrarenal angiotensin II levels in diabetic hamsters independently of blood pressure levels. In contrast, ramipril did not show such sufficient effects. These effects occurred in parallel with improvements in superoxide production and expression of NAD(P)H oxidase components [NAD(P)H oxidase 4 and p22 phox] in glomeruli. This study showed for the first time that chymase inhibition may protect against elevated intrarenal angiotensin II levels, oxidative stress, and renal dysfunction in diabetes. These findings suggest that chymase offers a new therapeutic target for diabetic nephropathy.

scholarly journals Angiotensin II and Angiotensin Receptors 1 and 2—Multifunctional System in Cells Biology, What Do We Know?

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 381
Author(s):  
Maksymilian Ziaja ◽  
Kinga Anna Urbanek ◽  
Karolina Kowalska ◽  
Agnieszka Wanda Piastowska-Ciesielska
Keyword(s):  
Angiotensin Ii ◽  
Cardiovascular System ◽  
Renin Angiotensin System ◽  
Angiotensin Receptors ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Individual ◽  
In Cells

For years, the renin-angiotensin system (RAS) has been perceived as a system whose role is to primarily modulate the functioning of the cardiovascular system. Years of research into the role of RAS have provided the necessary data to confirm that the role of RAS is very complex and not limited to the cardiovascular system. The presence of individual elements of the renin-angiotensin (RA) system allows to control many processes, ranging from the memorization to pro-cancer processes. Maintaining the proportions between the individual axes of the RA system allows for achieving a balance, often called homeostasis. Thus, any disturbance in the expression or activity of individual RAS elements leads to pathophysiological processes.

The Renin Angiotensin System and Bipolar Disorder: A Systematic Review

2020 ◽  
Vol 27 (6) ◽  
pp. 520-528 ◽  
Author(s):  
Izabela Guimarães Barbosa ◽  
Giulia Campos Ferreira ◽  
Diomildo Ferreira Andrade Júnior ◽  
Cássio Rocha Januário ◽  
André Rolim Belisário ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bipolar Disorder ◽  
Cardiovascular Diseases ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Angiotensin Receptors ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Search Terms

Bipolar Disorder (BD) is a chronic a multifactorial psychiatric illness that affects mood, cognition, and functioning. BD is associated with several psychiatric conditions as well clinical comorbidities, particularly cardiovascular diseases. The neurobiology of BD is complex and multifactorial and several systems have been implicated. Considering that the Renin Angiotensin System (RAS) plays an important role in cardiovascular diseases and that recently evidence has suggested its role in psychiatric disorders, the aim of the present study is to summarize and to discuss recent findings related to the modulation of RAS components in BD. A systematic search of the literature using the electronic databases MEDLINE and LILACS was conducted through March 2019. The search terms were: “Bipolar Disorder”; “Renin Angiotensin System”; “Angiotensin 2”; “Angiotensin receptors”; “Angiotensin 1-7”; “ACE”; “ACE2”; “Mas Receptor”. We included original studies assessing RAS in BD patients. Two hundred twenty-two citations were initially retrieved. Eleven studies were included in our systematic review. In the majority of studies (6 of 8), the ACE insertion/deletion (I/D) polymorphism did not differ between BD patients and controls. BD patients presented higher plasma renin activity in comparison with controls. The studies evaluating the RAS molecules in BD are very scarce and heterogeneous. The literature suggests a potential role of RAS in BD. Further studies are necessary to investigate this relationship.

Anti-Hypertensive Potential and Epigenetics of Angiotensin II type 2 Receptor (AT2R)

2020 ◽  
Vol 16 ◽  
Author(s):  
Mayank Chaudhary
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Blood Pressure Regulation ◽  
Biologically Active ◽  
Pressure Regulation ◽  
Tissue Remodelling ◽  
Critical Pathway

Background:: Renin angiotensin system (RAS) is a critical pathway involved in blood pressure regulation. Octapeptide, angiotensin II (Ang aII), is biologically active compound of RAS pathway which mediates its action by binding to either angiotensin II type 1 receptor (AT1R) or angiotensin II type 2 receptor (AT2R). Binding of Ang II to AT1R facilitates blood pressure regulation whereas AT2R is primarily involved in wound healing and tissue remodelling. Objective:: Recent studies have highlighted additional role of AT2R to counter balance detrimental effects of AT1R. Activation of angiotensin II type 2 receptor using AT2R agonist has shown effect on natriuresis and release of nitric oxide. Additionally, AT2R activation has been found to inhibit angiotensin converting enzyme (ACE) and enhance angiotensin receptor blocker (ARB) activity. These findings highlight the potential of AT2R as novel therapeutic target against hypertension. Conclusion:: The potential role of AT2R highlights the importance of exploring additional mechanisms that might be crucial for AT2R expression. Epigenetic mechanisms including DNA methylation and histone modification have been explored vastly with relation to cancer but role of such mechanisms on expression of AT2R has recently gained interest.

scholarly journals The Role of the FOXO1/β2-AR/p-NF-κB p65 Pathway in the Development of Endometrial Stromal Cells in Pregnant Mice under Restraint Stress

2021 ◽  
Vol 22 (3) ◽  
pp. 1478
Author(s):  
Jiayin Lu ◽  
Yaoxing Chen ◽  
Zixu Wang ◽  
Jing Cao ◽  
Yulan Dong
Keyword(s):  
Oxidative Stress ◽  
Stromal Cells ◽  
Restraint Stress ◽  
Target Genes ◽  
Mrna Levels ◽  
Endometrial Stromal Cells ◽  
Protein Levels ◽  
Pregnant Mice

Restraint stress causes various maternal diseases during pregnancy. β2-Adrenergic receptor (β2-AR) and Forkhead transcription factor class O 1 (FOXO1) are critical factors not only in stress, but also in reproduction. However, the role of FOXO1 in restraint stress, causing changes in the β2-AR pathway in pregnant mice, has been unclear. The aim of this research was to investigate the β2-AR pathway of restraint stress and its impact on the oxidative stress of the maternal uterus. In the study, maternal mice were treated with restraint stress by being restrained in a transparent and ventilated device before sacrifice on Pregnancy Day 5 (P5), Pregnancy Day 10 (P10), Pregnancy Day 15 (P15), and Pregnancy Day 20 (P20) as well as on Non-Pregnancy Day 5 (NP5). Restraint stress augmented blood corticosterone (CORT), norepinephrine (NE), and blood glucose levels, while oestradiol (E2) levels decreased. Moreover, restraint stress increased the mRNA levels of the FOXO family, β2-AR, and even the protein levels of FOXO1 and β2-AR in the uterus and ovaries. Furthermore, restraint stress increased uterine oxidative stress level. In vitro, the protein levels of FOXO1 were also obviously increased when β2-AR was activated in endometrial stromal cells (ESCs). In addition, phosphorylated-nuclear factor kappa-B p65 (p-NF-κB p65) and its target genes decreased significantly when FOXO1 was inhibited. Overall, it can be said that the β2-AR/FOXO1/p-NF-κB p65 pathway was activated when pregnant mice were under restraint stress. This study provides a scientific basis for the origin of psychological stress in pregnant women.

Androgens augment proximal tubule transport

2004 ◽  
Vol 287 (3) ◽  
pp. F452-F459 ◽  
Author(s):  
Albert Quan ◽  
Sumana Chakravarty ◽  
Jian-Kang Chen ◽  
Jian-Chun Chen ◽  
Samer Loleh ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Specific Binding ◽  
Extracellular Volume ◽  
Renin Angiotensin System ◽  
Angiotensin Receptors ◽  
Sprague Dawley ◽  
Angiotensin System ◽  
Renin Angiotensin

The proximal tubule contains an autonomous renin-angiotensin system that regulates transport independently of circulating angiotensin II. Androgens are known to increase expression of angiotensinogen, but the effect of androgens on proximal tubule transport is unknown. In this in vivo microperfusion study, we examined the effect of androgens on proximal tubule transport. The volume reabsorptive rate in Sprague-Dawley rats given dihydrotestosterone (DHT) injections was significantly higher than in control rats given vehicle injections (4.57 ± 0.31 vs. 3.31 ± 0.23 nl·min−1·mm−1, P < 0.01). Luminally perfusing with either enalaprilat (10−4 M) to inhibit production of angiotensin II or losartan (10−8 M) to block the angiotensin receptor decreased the proximal tubule volume reabsorptive rate in DHT-treated rats to a significantly greater degree than in control vehicle-injected rats. The renal expression of angiotensinogen was shown to be higher in the DHT-treated animals, using Northern blot analysis. The expression of angiotensin receptors, determined by specific binding of angiotensin II, was not different in the two groups of animals. Brush-border membrane protein abundance of the Na/H exchanger, a membrane transport protein under angiotensin II regulation, was also higher in DHT-treated rats vs. control rats. Rats that received DHT had higher blood pressures than the control rats but had no change in their glomerular filtration rate. In addition, serum angiotensin II levels were lower in DHT-treated vs. control rats. These results suggest that androgens may directly upregulate the proximal tubule renin-angiotensin system, increase the volume reabsorptive rate, and thereby increase extracellular volume and blood pressure and secondarily decrease serum angiotensin II levels.

scholarly journals The Effects of Central Angiotensin II and Its Specific Blockers on Nociception. Possible Interactions with Oxidative Stress Status / Efekti Centralnog Angiotenzina II I Njegovih Specifičnih Blokatora Na Nocicepciju. Moguće Interakcije Sa Statusom Oksidativnog Stresa

2013 ◽  
Vol 32 (1) ◽  
pp. 52-58 ◽  
Author(s):  
Oana Arcan ◽  
Alin Ciobica ◽  
Walther Bild ◽  
Bogdan Stoica ◽  
Lucian Hritcu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Analgesic Effect ◽  
Pain Perception ◽  
Ace Inhibitor ◽  
Renin Angiotensin System ◽  
Latency Time ◽  
Ang Ii ◽  
Hot Plate ◽  
At2 Receptors

SummaryIt has already been demonstrated that a complete brain renin-angiotensin system (RAS) exists distinctly separate from the peripheral system and is implicated in complex functions such as memory, emotional responses and pain. Regarding the implications of angiotensin II (the main bioactive peptide of RAS) in pain, although there are many studies in this area of research, most of the results are controversial. Also, it seems that oxidative stress follows angiotensin II infusion, but the role of AT1 vs. AT2 receptors is not well established. In this context, we were interested in studying the effects of central RAS on nociception, through the intracerebroventricular administration of losartan and PD-123177 (antagonists for the AT1/AT2 receptors), as well as an ACE inhibitor (captopril) and also angiotensin II in rats, which were subsequently tested using the hot-plate task, a well known behavioral test for pain perception. We present here the analgesic effect of angiotensin II administration, as shown by in creased latency-time in the hot-plate, as well as a nociceptive effect of angiotensin II blockers like AT1 and AT2 specific antagonists (losartan and PD-123177) and an ACE inhibitor (captopril), as their administration resulted in decreased latency-time. Moreover, we demonstrated a significant correlation between the results of the nociceptive behavioral task and the levels of some main oxidative stress markers. This provides additional evidence for an analgesic effect of Ang II administration, as well as for a nociceptive effect of Ang II blockers. Moreover, a significant correlation between the nociception and angiotensin II-induced oxidative stress is presented.

Thermal responses to central angiotensin II, SQ 20881, and dopamine infusions in sheep

1985 ◽  
Vol 248 (3) ◽  
pp. R371-R377 ◽  
Author(s):  
B. S. Huang ◽  
M. J. Kluger ◽  
R. L. Malvin
Keyword(s):  
Angiotensin Ii ◽  
Body Temperature ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Significant Rise ◽  
Ang Ii ◽  
Deep Body Temperature ◽  
Angiotensin System ◽  
Conscious Sheep

The thermoregulatory role of brain angiotensin II (ANG II) was tested by intracerebroventricular (IVT) infusion of ANG II or the converting enzyme inhibitor SQ 20881 (SQ) in 15 conscious sheep. Deep body temperature decreased 0.30 +/- 0.07 degree C (SE) during the 3-h period of IVT ANG II (25 ng/min) infusion (P less than 0.05) and increased 0.50 +/- 0.13 degree C during IVT SQ (1 microgram/min) infusion (P less than 0.01). To determine whether the rise in body temperature after IVT SQ infusion might be the result of a central renin-angiotensin system (RAS), SQ was infused IVT in five conscious sheep 20 h after bilateral nephrectomy. This resulted in a significant rise in body temperature of 0.28 +/- 0.05 degree C (P less than 0.05). When vasopressin antidiuretic hormone (ADH) was infused intravenously at the same time of IVT SQ infusion, the rise in temperature was depressed, but ADH did not lower the temperature below basal. IVT dopamine (20 micrograms/min) increased body temperature by 0.40 +/- 0.04 degree C (P less than 0.01), which was qualitatively similar to the result with IVT SQ. These data support the hypothesis that endogenous brain ANG II may play a role in thermoregulation. Furthermore, plasma ADH level, regulated in part by brain ANG II, is probably not the mediator of that thermoregulation. The similar effects of IVT dopamine and SQ on body temperature strengthen the hypothesis that dopamine may be involved in the central action of brain ANG II.

scholarly journals Açaí (Euterpe oleracea Mart.) seed extract protects against hepatic steatosis and fibrosis in high-fat diet-fed mice: Role of local renin-angiotensin system, oxidative stress and inflammation

2020 ◽  
Vol 65 ◽  
pp. 103726 ◽  
Author(s):  
Matheus Henrique Romão ◽  
Graziele Freitas de Bem ◽  
Izabelle Barcellos Santos ◽  
Ricardo de Andrade Soares ◽  
Dayane Teixeira Ognibene ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Renin Angiotensin System ◽  
Seed Extract ◽  
Euterpe Oleracea ◽  
High Fat ◽  
Angiotensin System ◽  
Euterpe Oleracea Mart

scholarly journals The resistant effect of SIRT1 in oxidative stress-induced senescence of rat nucleus pulposus cell is regulated by Akt-FoxO1 pathway

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Junsheng He ◽  
Ailiang Zhang ◽  
Zhiwen Song ◽  
Shiwu Guo ◽  
Yuwei Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nucleus Pulposus ◽  
Intervertebral Disc Degeneration ◽  
Nucleus Pulposus Cell ◽  
Sublethal Concentration ◽  
Action Mechanism ◽  
Protein Levels ◽  
Signaling Axis ◽  
Silent Information Regulator 1

Abstract Objective: The senescence of nucleus pulposus (NP) cells induced by oxidative stress is one of the important causes of intervertebral disc degeneration (IDD). Herein, we investigated the role and action mechanism of silent information regulator 1 (SIRT1) in oxidative stress-induced senescence of rat NP cell. Methods: Premature senescence of rat NP cells was induced by sublethal concentration of hydrogen peroxide (H2O2) (100 μM). SIRT1 was activated with SRT1720 (5 μM) to explore its effect on NP cells senescence. FoxO1 and Akt were inhibited by AS1842856 (0.2 μM) and MK-2206 (5 μM), respectively, to explore the role of Akt-FoxO1-SIRT1 axis in rat NP cells. Pretreatment with the resveratrol (20 μM), a common antioxidant and indirect activator of SIRT1, was done to investigate its role in senescent rat NP cells. Results: The mRNA and protein levels of SIRT1 were decreased in H2O2-induced senescent rat NP cells, and that specific activation of SIRT1 suppresses senescence. And the Akt-FoxO1 pathway, as the upstream of SIRT1, might be involved in the regulation of H2O2-induced senescence of rat NP cells by affecting the expression of SIRT1. In addition, the resveratrol played an anti-senescence role in rat NP cells, which might affect the Akt-FoxO1-SIRT1 axis. Conclusion: SIRT1 ameliorated oxidative stress-induced senescence of rat NP cell which was regulated by Akt-FoxO1 pathway, and resveratrol exerted anti-senescence effects by affecting this signaling axis.

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