scholarly journals Deficiency of Angiotensin Type 2 Receptor Rescues Obesity But Not Hypertension Induced by Overexpression of Angiotensinogen in Adipose Tissue

Endocrinology ◽  
2008 ◽  
Vol 150 (3) ◽  
pp. 1421-1428 ◽  
Author(s):  
Laurent Yvan-Charvet ◽  
Florence Massiéra ◽  
Noël Lamandé ◽  
Gérard Ailhaud ◽  
Michèle Teboul ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adipose Tissue ◽  
Angiotensin Ii ◽  
Fat Mass ◽  
Lipogenic Gene Expression ◽  
Angiotensin Type 2 Receptor ◽  
Adipocyte Hypertrophy ◽  
Angiotensin Type

Increased angiotensinogen (AGT) production by white adipose tissue has been related to not only obesity but also hypertension. Several studies have highlighted the importance of the angiotensin II type 2 receptor (AT2) in the regulation of blood pressure and fat mass, but the relevance of this transporter in a physiopathological model of increased AGT production, as it occurs in obesity, has not yet been investigated. We used transgenic mice that display either a deletion of AT2 (AT2 KO), an overexpression of AGT (OVEX), or both compound mutants (KOVEX). Results demonstrated that adipocyte hypertrophy and increased lipogenic gene expression induced by adipose AGT overproduction was rescued by deletion of AT2. In line with AGT overexpression, KOVEX and OVEX mice have similar increased plasma AGT levels. However, KOVEX mice display a higher blood pressure than OVEX mice. In kidney, renin expression was clearly reduced in OVEX mice, and its expression was normalized in KOVEX mice. Taken together, we demonstrated that the loss of AT2 expression was sufficient to rescue obesity induced by adipose tissue AGT overexpression and confirmed the necessary role of AT2 for the onset of obesity in this model. Furthermore, despite a reduction of adipose mass in KOVEX, AT2 deficiency caused increased renin production, further worsening the hypertension caused by AGT overexpression. Angiotensin type 2 receptor shows antihypertensive function but promotes the angiotensin II-mediated fat mass enlargement.

scholarly journals Pressor responsiveness to angiotensin II in female mice is enhanced with age: role of the angiotensin type 2 receptor

2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Katrina M Mirabito ◽  
Lucinda M Hilliard ◽  
Geoffrey A Head ◽  
Robert E Widdop ◽  
Kate M Denton
Keyword(s):  
Angiotensin Ii ◽  
Female Mice ◽  
Angiotensin Type 2 Receptor ◽  
Angiotensin Type

scholarly journals Reduced sensitivity of the renal vasculature to angiotensin II in young rats: the role of the angiotensin type 2 receptor

2014 ◽  
Vol 76 (5) ◽  
pp. 448-452 ◽  
Author(s):  
Russell D. Brown ◽  
Lucinda M. Hilliard ◽  
Katrina M. Mirabito ◽  
Laura C. Firth ◽  
Karen M. Moritz ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Renal Vasculature ◽  
Young Rats ◽  
Angiotensin Type 2 Receptor ◽  
Angiotensin Type

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 Activation of angiotensin type 2 receptor attenuates testosterone-induced hypertension and uterine vascular resistance in pregnant rats

2021 ◽  
Author(s):  
Jay S Mishra ◽  
Sathish Kumar
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Vascular Function ◽  
Uterine Artery ◽  
Artery Blood Flow ◽  
Protein Levels ◽  
Angiotensin Type 2 Receptor ◽  
Enos Protein ◽  
Angiotensin Type

Abstract Preeclampsia is a pregnancy-related hypertensive disorder with unclear mechanisms. While hypersensitivity to angiotensin II via vasoconstrictive angiotensin type-1 receptor (AT1R) is observed in preeclampsia, the importance of vasodilatory angiotensin type-2 receptor (AT2R) in the control of vascular dysfunction is less clear. We assessed whether AT1R, AT2R and eNOS expression is altered in placental vessels of preeclamptic women and tested if ex vivo incubation with AT2R agonist Compound 21 (C21; 1 μM) could restore AT1R, AT2R and eNOS balance. Further, using a rat model of gestational hypertension induced by elevated testosterone, we examined whether C21 (1 μg·kg−1·day−1, oral) could preserve AT1R and AT2R balance and improve blood pressure, uterine artery blood flow, and vascular function. Western blots revealed that AT1R protein level was higher while AT2R and eNOS protein were reduced in preeclamptic placental vessels, and AT2R agonist C21 decreased AT1R and increased AT2R and eNOS protein levels in preeclamptic vessels. In testosterone-dams, blood pressure was higher, and uterine artery blood flow was reduced, and C21 treatment reversed these levels similar to those in controls dams. C21 attenuated the exaggerated Ang II contraction and improved endothelium-dependent vasorelaxation in uterine arteries of testosterone-dams. These C21-mediated vascular effects were associated with decreased AT1R and increased AT2R and eNOS protein levels. C21 also increased serum nitrate/nitrite and bradykinin production in testosterone-dams and attenuated the feto-placental growth restriction. Thus, AT1R upregulation and AT2R downregulation is observed in preeclampsia and testosterone-model, and increasing AT2R activity could help restore AT1R and AT2R balance and improve gestational vascular function.

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 081: Reporter Mouse Strain Provides a Novel Look at Angiotensin Type-2 Receptor Distribution in Central Nervous System Cardiovascular Control Centers

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Annette D de Kloet ◽  
Lei Wang ◽  
Jacob A Ludin ◽  
Helmut Hiller ◽  
Justin A Smith ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Fluid Balance ◽  
Hypothalamic Nucleus ◽  
Reporter Mouse ◽  
Arterial Blood ◽  
Egfp Reporter ◽  
Angiotensin Type 2 Receptor ◽  
The Brain ◽  
Angiotensin Type

It is established that angiotensin-II acts at its type-1 receptor (AT1R) in the brain to increase sympathetic outflow and blood pressure, and modulate fluid balance. However, the role of the angiotensin type-2 receptor (AT2R) in the neural control of these processes has received far less attention, largely because of an inability to effectively localize these receptors at a cellular level in the brain. The present studies combine the use of a bacterial artificial chromosome transgenic AT2R-eGFP reporter mouse with recent advances in in situ hybridization (ISH) to circumvent this obstacle. Dual IHC/ ISH studies validated the AT2R-eGFP reporter mice by determining that eGFP and AT2R mRNA were highly co-localized within the nucleus of the solitary tract (NTS; 98.0 ± 0.18 %; 125 ± 3.6 of 127 ± 3.9 cells; n = 4). Analysis of eGFP immunoreactivity in the brain revealed localization to neurons within nuclei that regulate blood pressure and fluid balance (e.g., NTS and median preoptic nucleus [MnPO]). Additional IHC/ISH studies uncovered the phenotype of specific AT2R-eGFP cells. For example, within the NTS, AT2R-eGFP neurons primarily express glutamic acid decarboxylase-67 (GABAergic; 80 ± 2.8 %; 225 ± 12.5 of 280 ± 8.4 cells; n = 4), while only a subset express vesicular glutamate transporter-2 (glutamatergic; 18.2 ± 2.9 %; 50.8 ± 7.7 of 280 ± 8.4 cells) or AT1R (8.7 ± 1.0 %; 22 ± 2.2 of 256 ± 11.7 cells). No co-localization was observed with tyrosine hydroxylase in the NTS. Although AT2R-eGFP neurons were not observed within the paraventricular hypothalamic nucleus (PVN), eGFP was localized to efferents terminating in the PVN and to GABAergic neurons surrounding this nucleus. Retrograde neuronal tract tracing studies revealed that many eGFP-positive efferents to the PVN arise from neurons in the MnPO. Based on these neuroanatomical results, we hypothesized that activation of central AT2R would decrease blood pressure. Consistent with this hypothesis, chronic administration of the selective AT2R agonist, compound 21 (7.5 ng/h into the lateral cerebral ventricle) reduced baseline mean arterial blood pressure relative to control mice (103 ± 1.65 v. 110 ± 1.70 mmHg; n = 16; p = 0.02). These studies demonstrate that central AT2R are positioned to regulate blood pressure.

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