scholarly journals Interaction between Angiotensin Type 1, Type 2, and Mas Receptors to Regulate Adult Neurogenesis in the Brain Ventricular–Subventricular Zone

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1551 ◽  
Author(s):  
Maria Garcia-Garrote ◽  
Ana Perez-Villalba ◽  
Pablo Garrido-Gil ◽  
German Belenguer ◽  
Juan A. Parga ◽  
...  
Keyword(s):  
Adult Neurogenesis ◽  
Subventricular Zone ◽  
Functional Dependence ◽  
Renin Angiotensin System ◽  
At1 Receptor ◽  
Receptor Expression ◽  
At2 Receptor ◽  
Angiotensin Type

The renin–angiotensin system (RAS), and particularly its angiotensin type-2 receptors (AT2), have been classically involved in processes of cell proliferation and maturation during development. However, the potential role of RAS in adult neurogenesis in the ventricular-subventricular zone (V-SVZ) and its aging-related alterations have not been investigated. In the present study, we analyzed the role of major RAS receptors on neurogenesis in the V-SVZ of adult mice and rats. In mice, we showed that the increase in proliferation of cells in this neurogenic niche was induced by activation of AT2 receptors but depended partially on the AT2-dependent antagonism of AT1 receptor expression, which restricted proliferation. Furthermore, we observed a functional dependence of AT2 receptor actions on Mas receptors. In rats, where the levels of the AT1 relative to those of AT2 receptor are much lower, pharmacological inhibition of the AT1 receptor alone was sufficient in increasing AT2 receptor levels and proliferation in the V-SVZ. Our data revealed that interactions between RAS receptors play a major role in the regulation of V-SVZ neurogenesis, particularly in proliferation, generation of neuroblasts, and migration to the olfactory bulb, both in young and aged brains, and suggest potential beneficial effects of RAS modulators on neurogenesis.

Dopamine regulates adult neurogenesis in the ventricular‐subventricular zone via dopamine D3 angiotensin type 2 receptor interactions

Stem Cells ◽  
2021 ◽  
Author(s):  
Maria Garcia‐Garrote ◽  
Juan A. Parga ◽  
Pablo J. Labandeira ◽  
Jose Luis Labandeira‐Garcia ◽  
Jannette Rodriguez‐Pallares
Keyword(s):  
Adult Neurogenesis ◽  
Subventricular Zone ◽  
Angiotensin Type 2 Receptor ◽  
Receptor Interactions ◽  
Dopamine D3 ◽  
Angiotensin Type

The Role of Angiotensin-(1-7)/Mas Axis and Angiotensin Type 2 Receptors in the Central Nervous System in Cardiovascular Disease and Therapeutics: A Riddle to be Solved

2019 ◽  
Vol 17 (4) ◽  
pp. 319-325 ◽  
Author(s):  
Vasiliki Katsi ◽  
Spyridon Maragkoudakis ◽  
Maria Marketou ◽  
Costas Tsioufis ◽  
Fragkiskos Parthenakis ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Experimental Studies ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Pressure Lowering ◽  
The Central Nervous System ◽  
Novel Therapeutic Strategies ◽  
Angiotensin Type

: In recent years, the Angiotensin-(1-7)/Mas receptor [Ang-(1-7)/Mas] sub-branch of the Renin-Angiotensin System (RAS) in the brain, and Angiotensin Type 2 Receptors (AT2R), have attracted scientific interest, as there is evidence that they constitute an essential pathway in cardiovascular regulation, in health and in disease. By acting centrally, the Ang-(1-7)/Mas axis - that has been termed ‘the axis of good’- can exert blood pressure-lowering effects, while also favourably altering baroreflex sensitivity and noradrenergic neurotransmission. Thus, research has focused on the possible neuro- and cardioprotective effects of this pathway in the setting of cardiovascular disease, ultimately aiming to evaluate the potential for development of novel therapeutic strategies based on its modulation. : We summarize the available evidence from experimental studies in this context, aiming to assess current limits of scientific knowledge relevant to this newly-described ‘player’ in haemodynamic regulation, that may become a potential therapeutic target.

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.

Estrogen Deficiency and Colonic Function: Surgical Menopause and Sex Differences in Angiotensin and Dopamine Receptor Interaction

2020 ◽  
Author(s):  
Pablo Garrido-Gil ◽  
Ana I Rodriguez-Perez ◽  
Lucia Lage ◽  
Jose L Labandeira-Garcia
Keyword(s):  
Sex Differences ◽  
Dopamine Receptors ◽  
D2 Receptor ◽  
Renin Angiotensin System ◽  
Receptor Expression ◽  
Oxidative Markers ◽  
Mutual Regulation ◽  
Inflammatory Processes ◽  
Angiotensin Type

Abstract The physiopathological mechanisms that regulate menopausal and sex differences in colonic transit, inflammatory processes, and efficacy of treatments have not been clarified. The dopaminergic system and renin–angiotensin system coexist in the gut and regulate different processes such as motility, absorption/secretion, and inflammation. We investigated the changes in expression of major angiotensin and dopamine receptors in the colon of male, female, and ovariectomized female mice. Possible interaction between both systems was investigated using male and female mice deficient (ko) for major angiotensin and dopamine receptors. In wild-type mice, colonic tissue from females showed lower angiotensin type 1/angiotensin type 2 ratio (an index of pro-inflammatory/anti-inflammatory renin–angiotensin system balance), lower dopamine D1 and D2 receptor expression, and lower levels of pro-inflammatory and pro-oxidative markers relative to males. Interestingly, ovariectomy increased the expression of pro-inflammatory angiotensin type 1 receptor expression and decreased anti-inflammatory angiotensin type 2 receptor expression, increased D1 and D2 receptor expression, and increased the levels of pro-inflammatory and pro-oxidative markers. Ovariectomy-induced changes were blocked by estrogen replacement. The present results suggest a mutual regulation between colonic angiotensin and dopamine receptors and sex differences in this mutual regulation. Estrogen regulates changes in both angiotensin and dopamine receptor expression, which may be involved in sex- and surgical menopause-related effects on gut motility, permeability, and vulnerability to inflammatory processes.

Abstract 309: Sp-3 But not the NF-kB Transcription Factor Causes the Up-regulation of Angiotensin Type 1 Receptor Expression and Contributes to Hypertension in Aging FBN rats.

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Mohammad Saleem ◽  
Mohammad Asghar
Keyword(s):  
Blood Pressure ◽  
Transcription Factors ◽  
At1 Receptor ◽  
Receptor Expression ◽  
Receptor Protein ◽  
Receptor Function ◽  
Receptor Mrna ◽  
Hk2 Cells ◽  
Angiotensin Type

We recently reported that age-associated oxidative stress is causal to higher renal angiotensin Type 1 (AT1) receptor function and hypertension in aged Fisher 344 X Brown Norway (FBN) rats. We became interested in examining the mechanism of higher AT1 receptor function in the aging kidneys. Adult (3-month) and aging (21 month) FBN rats were subjected to conscious blood pressure measurement by telemetry approach. The levels of AT1 receptor mRNA in the kidney cortex was measured by qRT-PCR while nuclear Sp-3 and NF-kB-p65 redox-sensitive transcription factors were determined by western blotting. We found that blood pressure was higher in aged than in adult rats (adult vs. old: 110±1 vs. 130±1 mmHg) which was associated with higher AT1 receptor mRNA levels (adult vs. old: 1.51±0.72 vs. 7.86±1.03 DU), and nuclear levels of both Sp-3 (adult vs. old: 0.56±.01 vs. 1.54±.02 DU) and NF-kB-p65 (adult vs. old: 0.9±.01 vs. 1.5±0.01 DU). To further delineate whether sp-3 or NF-kB-p65 or both transcription factors are responsible for the up-regulation of AT1 receptor, human kidney (HK2) cells were transfected with Sp-3 and NF-kB-p65 plasmids. We found that Sp-3 plasmid but not NF-κB-p65 plasmid transfection caused an increase in the levels of AT1 receptor protein in HK2 cells (control vs. transfected: 135±22 vs. 235±10 DU). Furthermore, Sp-3 siRNA treatment resulted in the reduction of Sp-3 (control vs. transfected: 136±10 vs. 93±21 DU) and AT1 receptor protein levels (control vs. transfected: 270±38 vs. 172±201 DU) in HK2 cells. Our results suggest that sp-3 but not the NF-κB-p65 is involved in the up-regulation of renal AT1 receptor that may be contributing to hypertension in aging FBN rats.

Abstract P288: Systemic Administration of an Angiotensin Type-2 Receptor Agonist Decreases Renal Regulatory T Cells

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Ellen E Gillis ◽  
Jennifer C Sullivan
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Critical Role ◽  
High Dose ◽  
Ang Ii ◽  
Osmotic Minipump ◽  
Angiotensin Type 2 Receptor ◽  
Angiotensin Type

There is increasing evidence supporting a critical role of the immune system in the development of hypertension. Our lab has previously reported sex differences in the renal T cell profile in both Spontaneously Hypertensive Rats (SHR) and Angiotensin II (Ang II) models of hypertension, with females having more anti-inflammatory regulatory T cells (Tregs) than males. Ang II has a well-defined role in the activation of pro-inflammatory T cells in hypertension via the angiotensin type-1 receptor (AT1R). Less is known about the role of the angiotensin type-2 receptor (AT2R) in the regulation of immune cells, although the AT2R has been shown to be cardioprotective and AT2R expression is greater in females than males. Based on the potential anti-hypertensive role of AT2Rs, we hypothesized that administration of an AT2R agonist, Compound 21 (C21), would increase renal Tregs, and this increase would be greater in females due to greater AT2R expression. Male and female SHR (10 weeks of age, n=3-4) were implanted with telemetry units for continuous monitoring of mean arterial pressure (MAP). Following 10 days of recovery, baseline MAP was recorded for 5 days. Rats were then divided into the following treatment groups: surgical controls, low dose C21 (150 ng/kg/min, sc by osmotic minipump), high dose C21 (300 ng/kg/min, sc by osmotic minipump). Kidneys were harvested after 2 weeks of treatment and flow cytometry was performed on whole kidney homogenates. MAP was not altered by C21 treatment in males (137±4 vs 134±4 vs 134±4 mmHg; n.s.) or females (128±2 vs 136±5 vs 134±4 mmHg; n.s.). Interestingly, despite having no effect on MAP, there was a significant decrease in renal CD3 + CD4 + FoxP3 + Tregs in females following both low and high doses of C21 (data expressed as % CD3 + CD4 + cells: 6±0.6 vs 3±0.6 vs 3.5±1.3 %, respectively; p=0.02). Tregs decrease in males following the high dose of C21 only (data expressed as % CD3 + CD4 + cells: 3.3±0.3 vs 3.3±0.5 vs 1.7±0.7 %, respectively; p=0.05). Total CD3 + T cells, CD3 + CD4 + T cells, and Th17 cells were not altered by C21 treatment. In conclusion, AT2R activation suppresses renal Tregs, and females are more sensitive than males. These data suggest a novel role for AT2R regulation in the kidney in hypertension.

Abstract 336: Angiotensinogen Gene Polymorphism Confers a Multiple Risk Factor for Atherosclerosis and Its Susceptibility Traits

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Nduna Dzimiri ◽  
Samar Elhawari ◽  
Mohammed Al-Najai ◽  
Paul Muiya ◽  
Daisy Gueco ◽  
...  
Keyword(s):  
Gene Polymorphism ◽  
Significant Risk ◽  
Renin Angiotensin System ◽  
Systemic Blood Pressure ◽  
Multiple Risk Factor ◽  
Systemic Blood ◽  
Angiotensin System ◽  
Cardiovascular Functions

Angiotensinogen (AGT) constitutes a pivotal component of the renin-angiotensin system which controls the systemic blood pressure and several other cardiovascular functions. In order to evaluate the role of the AGT gene polymorphism in atherosclerosis (CAD) and its risk factors, we first sequenced the gene in 200 individuals in search of informative SNPs. Of the >100 SNPs identified, we proceeded to evaluate the association of 8 variants in 3232 CAD cases versus 2292 angiographed controls by the Applied Biosystems real-time PCR system. Of the studied variants, the recessive mode of inheritance (TT) of rs3789679C>T [Odds ratio(95% Confidence Interval) = 1.23(1.05-1.45); p=0.012]; TT of rs699C>T [1.21(1.11-1.32); p<0.0001] as well as the dominant models (AG+GG) of rs5051A>G [1.22(1.10-1.37; p<0.0001) and AG+GG of rs2067853A>G [1.23(1.07-140);p=0.003] conferred risk for CAD. Interestingly, rs699 (p<0.0001), rs5051 (p=0.003) and rs2067853 (p=0.001) were equally implicated in hypertension, while the rs699 was further associated with hypercholesterolaemia (p=0.002) and hypertriglyceridaemia (p<0.0001), and the rs5051 was similarly associated with type 2 diabetes mellitus (T2DM) (p=0.011). One 8-mer haplotype from the 8 studied SNPs ACGGATAT (χ 2 =9.83; p=0.0017) and several of its variants, including the 7-mer ACGGATA (χ 2 =9.40; p=0.0022), 6-mer GGATAT (χ 2 =11.54; p=0.0007) and 5-mer GATAT (χ 2 =10.89; p=0.001) conferred significant risk for CAD. Furthermore, three 8-mer haploptypes GTGGGTGG (χ 2 =6.96; p=0.0083), ACGGGTAT (χ 2 =4.70; p=0.030) and GTAGGCGG (χ 2 =5.69; p=0.017) were associated with HTN. Similar trends were also observed for T2DM, obesity and hyperlipidaemia. These observations show that the AGT gene polymorphism confers a common risk for atherosclerosis and its major susceptibility traits.

scholarly journals Role of Oxidant Stress on AT1 Receptor Expression in Neurons of Rabbits With Heart Failure and in Cultured Neurons

2008 ◽  
Vol 103 (2) ◽  
pp. 186-193 ◽  
Author(s):  
Dongmei Liu ◽  
Lie Gao ◽  
Shyamal K. Roy ◽  
Kurtis G. Cornish ◽  
Irving H. Zucker
Keyword(s):  
Heart Failure ◽  
Oxidant Stress ◽  
At1 Receptor ◽  
Receptor Expression ◽  
Cultured Neurons

scholarly journals Angiotensin II Dilates Bovine Adrenal Cortical Arterioles: Role of Endothelial Nitric Oxide

Endocrinology ◽  
2005 ◽  
Vol 146 (8) ◽  
pp. 3319-3324 ◽  
Author(s):  
Kathryn M. Gauthier ◽  
David X. Zhang ◽  
Erik M. Edwards ◽  
Blythe Holmes ◽  
William B. Campbell
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cell ◽  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Receptor Activation ◽  
At1 Receptor ◽  
Internal Diameter ◽  
No Production ◽  
At2 Receptor ◽  
Angiotensin Type

Abstract Adrenal steroidogenesis is modulated by humoral and neuronal factors and blood flow. Angiotensin II (AII) stimulates adrenal cortical aldosterone and cortisol production and medullary catecholamine release. However, AII regulation of adrenal vascular tone has not been characterized. We examined the effect of AII on diameters of cannulated bovine adrenal cortical arteries. Cortical arteries (average internal diameter = 230 μm) were constricted with U46619 and concentration-diameter responses to AII (10−13 to 10−8 mol/liter) were measured. In endothelium-intact arteries, AII induced dilations at low concentrations (maximum dilation = 25 ± 6% at 10−10 mol/liter) and constrictions at high concentrations (maximum constriction = 25 ± 18% at 10−8 mol/liter). AII constrictions were blocked by the angiotensin type 1 (AT1) receptor antagonist, losartan (10−6 mol/liter). AII dilations were enhanced by losartan (maximal dilation = 48 ± 8%), abolished by endothelial cell removal or N-nitro-l-arginine (L-NA, 3 × 10−5 mol/liter) and inhibited by the angiotensin type 2 (AT2) receptor antagonist, PD123319 (10−6 mol/liter, maximal dilation = 18 ± 4%). In a 4,5-diaminofluorescein diacetate nitric oxide (NO) assay of isolated cortical arteries, AII stimulated NO production, which was abolished by PD123319, L-NA, or endothelial cell removal. Western immunoblot of arterial homogenates and endothelial and zona glomerulosa cell lysates revealed 48-kD and 50-kD bands corresponding to AT1 and AT2 receptors, respectively, in all three and a 140-kD band corresponding to endothelial NO synthase in endothelial cells and arteries. Our results demonstrate that AII stimulates adrenal cortical arterial dilation through endothelial cell AT2 receptor activation and NO release and AT1 receptor-dependent constriction.

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