Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptor

Nature ◽  
1995 ◽  
Vol 377 (6551) ◽  
pp. 748-750 ◽  
Author(s):  
Toshihiro Ichiki ◽  
Patricia A. Labosky ◽  
Chiyo Shiota ◽  
Shigeru Okuyama ◽  
Yasuko Imagawa ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Exploratory Behaviour

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.

Abstract 476: Renal AT2 Receptor Activation Prevents Sodium Retention And Lowers Blood Pressure In Angiotensin II-Dependent Hypertension

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Shetal H Padia ◽  
Nancy L Howell ◽  
Brandon A Kemp ◽  
John J Gildea ◽  
Susanna R Keller ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Receptor Activation ◽  
Pressure Probe ◽  
Ang Ii ◽  
Induced Hypertension ◽  
Group 5 ◽  
Group 2 ◽  
Angiotensin Type

A major proposed mechanism for the initiation of hypertension involves a primary increase in renal tubular sodium (Na+) reabsorption. Activation of intrarenal angiotensin type-2 receptors (AT2R) increases Na+ excretion; however, the role of intrarenal angiotensin type-2 receptors (AT2R) in the development of hypertension is unknown. Sprague-Dawley rats (N=36) underwent uninephrectomy and telemetric blood pressure probe implantation. Following a 72h recovery, two osmotic minipumps were inserted in each rat, one for chronic systemic delivery of 5% dextrose in water (D5W) or angiotensin II (Ang II, 200 ng/kg/min), and one for chronic intrarenal delivery of D5W (0.25 μL/h x 7d), highly selective AT2R agonist Compound 21 (C-21; 60 ng/kg/min x 7d), or specific AT2R antagonist PD-1223319 (PD; 10 ng/kg/min x 7d). Five groups of rats were studied: Group 1 (Control; N=10): systemic D5W + intrarenal D5W; Group 2 (Ang II-induced hypertension; N=8): systemic Ang II + intrarenal D5W; Group 3 (N=6): systemic Ang II + intrarenal C-21; Group 4 (N=6): systemic Ang II + 48h lead-in intrarenal C-21; Group 5 (N=6): systemic Ang II + intrarenal PD. Systemic Ang II infusion increased mean systolic blood pressure from 126±5 to 190±3 mm Hg over a 7d period in Group 2 (ANOVA F=73; P<1 X 10-6). Intrarenal administration of AT2R agonist C-21 (Groups 3 and 4) markedly inhibited the pressor effect of systemic Ang II (P<0.0001). Intrarenal AT2R antagonist PD (Group 5) augmented the pressor action of Ang II (P<0.0001). Consecutive 24h urinary Na+ excretion (UNaV) was reduced from 0.95±0.04 to 0.34±0.07 μmol/min (P<0.0001) on day 1 of Ang II infusion; Ang II-induced antinatriuresis was inhibited by intrarenal C-21 (P<0.0001) and augmented by intrarenal PD (P<0.0001) during the entire 7d infusion, demonstrating that one of the mechanisms to prevent Ang II-induced hypertension during intrarenal AT2R activation is the abolition of the initial increase in Na+ reabsorption that triggers the hypertensive cascade in this model. Thus, renal AT2Rs represent a novel therapeutic target for the prevention of hypertension.

Abstract 7: Angiotensin II Type 2 Receptor Deficiency Increases Renal ACE/ACE2 Ratio-Ang II-AT1R Expression In Male but not in Female Mice

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Quaisar Ali ◽  
Yonnie Wu ◽  
Tadashi Inagami ◽  
Tahir Hussain
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Angiotensin Ii ◽  
Renin Activity ◽  
Ang Ii ◽  
Male And Female ◽  
Female Mice ◽  
Gender Specific

Angiotensin II acting via Angiotensin II type 2 receptors (AT2Rs) is believed to be protective against blood pressure increase and affects renal function under pathophysiological condition. Recently we have observed that stimulation of AT2Rs in male obese Zucker rats has shifted the two opposing arms of renin angiotensin system (RAS) i.e. ACE-Ang II-AT1 vs ACE2/Ang-(1-7)-Mas. Evidence suggests that estrogen regulates RAS, including AT2R in female mice. We hypothesized that AT2R has a gender specific regulation of RAS. In the present study, we investigated the role of AT2Rs in regulating RAS components in male and female mice. Kidney cortex from AT2R knockout (AT2RKO) male and female mice and wild type (WT) with similar background (C57BL/6) of 20 weeks of age were used in the study. The cortical ACE expression (ng ACE/μg tissue) was significantly increased in AT2RKO mice (3±0.02) compared to WT males (1.9±0.02). LC/MS analysis of cortical tissue revealed that Ang II was also significantly increased in AT2RKO mice (WT: 31±3, AT2RKO: 47±3 fmoles/mg tissue). Deletion of AT2R significantly increased AT1R (204%, 204 of 100) expression and had no effect on renin activity compared to WT males. The cortical expression of ACE2 activity (WT: 113±8, AT2RKO: 40±11, RFU/min), Ang-(1-7) levels (WT: 7.3±1.4, AT2RKO: 3±0.8 fmoles/mg tissue) and Mas receptor (AT2RKO: 54±15, % of WT) was significantly decreased in AT2RKO males compared to WT. The cortical expression of the AT2R and MasR was 2-fold greater in WT females compared to WT male. The renin activity (WT: 32±2, AT2RKO: 21±0.3, RFU/min) and MasR expression (WT: 187.5±55, AT2KO: 47±9) was significantly decreased in AT2RKO females compared to the female WT. Interestingly, Ang-(1-7) level (WT: 5.7±0.7, AT2RKO 2.6±0.7 fmoles/mg tissue) was decreased but no changes in ACE or ACE2 activity was observed in AT2KO females compared to their WT, suggesting a role of non-ACE2 pathway. This study suggests that AT2R regulates ACE/ACE2 ratio-Ang II-AT1R expression negatively only in males, whereas in females, it regulates Ang-(1-7) potentially via non-ACE2 pathway. Such changes indicate a gender specific mechanisms potentially associated with AT2R-mediated regulation of renal function and blood pressure control.

scholarly journals Rosiglitazone, a Ligand to PPARγ, Improves Blood Pressure and Vascular Function through Renin-Angiotensin System Regulation

PPAR Research ◽  
2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
María Sánchez-Aguilar ◽  
Luz Ibarra-Lara ◽  
Leonardo Del Valle-Mondragón ◽  
María Esther Rubio-Ruiz ◽  
Alicia G. Aguilar-Navarro ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
In Silico ◽  
Vascular Function ◽  
Renin Angiotensin System ◽  
Dependent Manner ◽  
Insulin Sensitizer ◽  
Angiotensin System ◽  
Renin Angiotensin

Rosiglitazone (RGZ), a peroxisome proliferator-activated receptor gamma (PPARγ) ligand, has been reported to act as insulin sensitizer and exert cardiovascular actions. In this work, we hypothesized that RGZ exerts a PPARγ–dependent regulation of blood pressure through modulation of angiotensin-converting enzyme (ACE)-type 2 (ACE2)/angiotensin-(1-7)/angiotensin II type-2 receptor (AT2R) axis in an experimental model of high blood pressure. We carried on experiments in normotensive (Sham) and aortic coarctation (AoCo)-induced hypertensive male Wistar rats. Both sham and AoCo rats were treated 7 days with vehicle (V), RGZ (5 mg/kg/day), or RGZ+BADGE (120 mg/kg/day) post-coarctation. We measured blood pressure and vascular reactivity on aortic rings, as well as the expression of renin-angiotensin system (RAS) proteins. We found that RGZ treatment in AoCo group decreases blood pressure values and improves vascular response to acetylcholine, both parameters dependent on PPARγ-stimulation. RGZ lowered serum angiotensin II (AngII) but increased Ang-(1-7) levels. It also decreased 8-hydroxy-2′-deoxyguanosine (8-OH-2dG), malondialdehyde (MDA), and improved the antioxidant capacity. Regarding protein expression of RAS, RGZ decreases ACE and angiotensin II type 1 receptor (AT1R) and improved ACE2, AT2R, and Mas receptor in AoCo rats. Additionally, an in silico analysis revealed that 5′UTR regions of RAS and PPARγ share motifs with a transcriptional regulatory role. We conclude that RGZ lowers blood pressure values by increasing the expression of RAS axis proteins ACE2 and AT2R, decreasing the levels of AngII and increasing levels of Ang-(1-7) in a PPARγ-dependent manner. The in silico analysis is a valuable tool to predict the interaction between PPARγ and RAS.

scholarly journals Management of Home Blood Pressure by Amlodipine Combined With Angiotensin II Receptor Blocker in Type 2 Diabetes

2012 ◽  
Vol 76 (9) ◽  
pp. 2159-2166 ◽  
Author(s):  
Katsumi Miyauchi ◽  
Tsutomu Yamazaki ◽  
Hirotaka Watada ◽  
Yasushi Tanaka ◽  
Ryuzo Kawamori ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Angiotensin Ii ◽  
Home Blood Pressure ◽  
Receptor Blocker ◽  
Angiotensin Ii Receptor Blocker ◽  
Angiotensin Ii Receptor

scholarly journals Angiotensin II Type 2 Receptor

Hypertension ◽  
2021 ◽  
Author(s):  
Naureen Fatima ◽  
Sanket N. Patel ◽  
Tahir Hussain
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Kidney Diseases ◽  
Gene Knockout ◽  
The Body ◽  
Sodium Reabsorption ◽  
Ang Ii ◽  
Organ Protection ◽  
Organ Systems

The renin-angiotensin system is of vital significance not only in the maintenance of blood pressure but also because of its role in the pathophysiology of different organ systems in the body. Of the 2 Ang II (angiotensin II) receptors, the AT 1 R (Ang II type 1 receptor) has been extensively studied for its role in mediating the classical functions of Ang II, including vasoconstriction, stimulation of renal tubular sodium reabsorption, hormonal secretion, cell proliferation, inflammation, and oxidative stress. The other receptor, AT 2 R (Ang II type 2 receptor), is abundantly expressed in both immune and nonimmune cells in fetal tissue. However, its expression is increased under pathological conditions in adult tissues. The role of AT 2 R in counteracting AT 1 R function has been discussed in the past 2 decades. However, with the discovery of the nonpeptide agonist C21, the significance of AT 2 R in various pathologies such as obesity, hypertension, and kidney diseases have been examined. This review focuses on the most recent findings on the beneficial effects of AT 2 R by summarizing both gene knockout studies as well as pharmacological studies, specifically highlighting its importance in blood pressure regulation, obesity/metabolism, organ protection, and relevance in the treatment of coronavirus disease 2019 (COVID-19).

scholarly journals Lifestyle intervention might easily improve blood pressure in hypertensive men with the C genotype of angiotensin II type 2 receptor gene

2015 ◽  
Vol 9 (4) ◽  
pp. 385 ◽  
Author(s):  
Kaori Kitaoka ◽  
Azusa Kitade ◽  
Junko Nagaoka ◽  
Kokoro Tsuzaki ◽  
Kiyomi Harada ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Lifestyle Intervention ◽  
Receptor Gene

scholarly journals Loss of Angiotensin II Type 2 Receptor Improves Blood Pressure in Elastin Insufficiency

2021 ◽  
Vol 8 ◽  
Author(s):  
Michelle Lin ◽  
Robyn A. Roth ◽  
Beth A. Kozel ◽  
Robert P. Mecham ◽  
Carmen M. Halabi
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Systolic Hypertension ◽  
Mesenteric Arteries ◽  
Large Artery ◽  
Ample Evidence ◽  
Artery Stiffness

There is ample evidence supporting a role for angiotensin II type 2 receptor (AT2R) in counterbalancing the effects of angiotensin II (ang II) through the angiotensin II type 1 receptor by promoting vasodilation and having anti-inflammatory effects. Elastin insufficiency in both humans and mice results in large artery stiffness and systolic hypertension. Unexpectedly, mesenteric arteries from elastin insufficient (Eln+/−) mice were shown to have significant vasoconstriction to AT2R agonism in vitro suggesting that AT2R may have vasoconstrictor effects in elastin insufficiency. Given the potential promise for the use of AT2R agonists clinically, the goal of this study was to determine whether AT2R has vasoconstrictive effects in elastin insufficiency in vivo. To avoid off-target effects of agonists and antagonists, mice lacking AT2R (Agtr2−/Y) were bred to Eln+/− mice and cardiovascular parameters were assessed in wild-type (WT), Agtr2−/Y, Eln+/−, and Agtr2−/Y;Eln+/− littermates. As previously published, Agtr2−/Y mice were normotensive at baseline and had no large artery stiffness, while Eln+/− mice exhibited systolic hypertension and large artery stiffness. Loss of AT2R in Eln+/− mice did not affect large artery stiffness or arterial structure but resulted in significant reduction of both systolic and diastolic blood pressure. These data support a potential vasocontractile role for AT2R in elastin insufficiency. Careful consideration and investigation are necessary to determine the patient population that might benefit from the use of AT2R agonists.

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