scholarly journals Selective Inhibition of the Renal Angiotensin Type 2 Receptor Increases Blood Pressure in Conscious Rats

Hypertension ◽  
2001 ◽  
Vol 37 (5) ◽  
pp. 1285-1291 ◽  
Author(s):  
Allan F. Moore ◽  
Nicolas T. Heiderstadt ◽  
Esther Huang ◽  
Nancy L. Howell ◽  
Zhi-Qin Wang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Selective Inhibition ◽  
Conscious Rats ◽  
Angiotensin Type 2 Receptor ◽  
Angiotensin Type

scholarly journals Angiotensin Type 2 Receptor Mediates Valsartan-Induced Hypotension in Conscious Rats

Hypertension ◽  
2000 ◽  
Vol 35 (5) ◽  
pp. 1074-1077 ◽  
Author(s):  
Helmy M. Siragy ◽  
Marc de Gasparo ◽  
Robert M. Carey
Keyword(s):  
Induced Hypotension ◽  
Conscious Rats ◽  
Angiotensin Type 2 Receptor ◽  
Angiotensin Type

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 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.

scholarly journals Activation of Central Angiotensin Type 2 Receptors Suppresses Norepinephrine Excretion and Blood Pressure in Conscious Rats

2011 ◽  
Vol 24 (6) ◽  
pp. 724-730 ◽  
Author(s):  
Juan Gao ◽  
Hao Zhang ◽  
Khang D. Le ◽  
Jie Chao ◽  
Lie Gao
Keyword(s):  
Blood Pressure ◽  
Conscious Rats ◽  
Angiotensin Type

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.

Abstract 073: Hindbrain Angiotensin Type-2 Receptors and Hypertension

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Annette D de Kloet ◽  
Lei Wang ◽  
Jacob A Ludin ◽  
Helmut Hiller ◽  
Justin A Smith ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Neural Control ◽  
Fluorescent Protein ◽  
Mrna Levels ◽  
Blood Pressure Lowering ◽  
Gaba Neurons ◽  
Angiotensin Type 2 Receptor ◽  
Pressure Lowering ◽  
Angiotensin Type

The role of the angiotensin type-2 receptor (AT2R) in the neural control of cardiovascular homeostasis and hypertension is not well-characterized. Using a BAC transgenic AT2R-enhanced green fluorescent protein (eGFP) reporter mouse, dense localization of AT2R to GABA neurons was found within the nucleus of the solitary tract (NTS) of the hindbrain, an area important for regulating baroreflex function and blood pressure. This localization was confirmed by RNAscope fluorescence in situ hybridization. Considering that GABA is pressor in the intermediate NTS (intNTS), and that its effects are enhanced in models of neurogenic hypertension such as SHR and deoxycorticosterone acetate (DOCA)-salt rats, we tested the hypothesis that AT2R on GABA neurons in the NTS constitute a counter-regulatory, blood pressure lowering mechanism. In support of this idea, we have demonstrated that: (i) Optogenetic stimulation of GABA neurons in the intNTS of normal mice elicited a significant increase in blood pressure; (ii) mRNA levels for both the GABA synthetic enzyme Gad1 and for the AT2R are significantly increased in the intNTS of DOCA-salt hypertensive mice; (iii) Intracerebroventricular (ICV) infusion of the AT2R agonist Compound 21 (C21; 7.5 ng/h) into normotensive or DOCA-salt hypertensive mice elicited a significant reduction of systolic blood pressure, an effect that was much larger in hypertensive (126.2 ± 5.0 v. 139.8 ± 3.2 mmHg; n = 14; p = 0.02) than in normotensive (119.8 ± 2.6 v. 126.5 ± 2.5 mmHg; n = 16; p = 0.04) mice and was accompanied by decreased levels of the GABA synthetic enzymes Gad1 and Gad2 in the intNTS; (iv) Finally, the crucial involvement of GABA neurons in the blood pressure lowering effect of AT2R was proven by the lack of any effect of ICV C21 in DOCA-salt hypertensive mice containing a selective knockout of AT2R from GABA neurons. These novel data provide strong evidence for an anti-hypertensive action of AT2R within the intNTS, an effect that is exerted through decreases in GABA transmission.

Abstract WMP84: Intranasal Trans-olfactory Delivery of the Angiotensin Type 2 Receptor Agonist Compound 21 is Neuroprotective in Ischemic Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Douglas M Bennion ◽  
Jacob D Isenberg ◽  
Alex N Dang ◽  
Chad H Jones ◽  
Justin T Graham ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Ischemic Stroke ◽  
Locomotor Activity ◽  
Post Stroke ◽  
Sd Rats ◽  
Angiotensin Type 2 Receptor ◽  
Compound 21 ◽  
Angiotensin Type

Background: Compound 21 (C21), a selective small-molecule angiotensin type 2 receptor (AT2R) agonist, has been proven in multiple preclinical studies to reduce infarct size and ameliorate neurological deficits, when administered after ischemic stroke via intracerebroventricular or intraperitoneal routes. However, C21 poorly penetrates the blood brain barrier (BBB). In this study, we used the novel and non-invasive approach of intranasal trans-olfactory (INTO) application, in order to bypass the BBB and deliver C21 directly into the brain. The therapeutic efficacy of INTO application of C21 was assessed in a model of transient middle cerebral artery occlusion (MCAO). Methods: (i) Male SD rats (12 weeks old) underwent ischemic stroke by endothelin-1-induced MCAO. They were randomly divided into two treatment groups, either receiving 0.9% saline or C21 (1.5 ug/kg) at 1.5, 4, 24 and 48 h post-stroke, using a rat intranasal catheter device (Impel Neuropharma, Seattle, WA) for INTO application. All rats underwent blinded neurological assessments at 4, 24 and 72 h after stroke, and immediately after the 72 h tests, were euthanized and cerebral infarct volumes were assessed by TTC staining. (ii) Male SD rats (12 weeks old) underwent implantation of a telemetry transducer (DSI, St. Paul, MN) into the abdominal aorta for measurement of blood pressure, heart rate and locomotor activity after INTO C21 (1.5 ug/kg) vs. 0.9% saline at baseline and post-ischemic stroke. Results: (i) Post-stroke INTO delivery of C21 (1.5 ug/kg) elicited a significant lowering of % cerebral infarct volume (25.4 ± 4.7; n=9) compared with saline-treated rats (48.4 ± 4.4; n=21) [p<0.05; two-way Mann-Whitney test]. The C21 (1.5 ug/kg)-treated rats also displayed highly significant improvements in Garcia and Bederson neurological scores (p<0.01; two-way Mann-Whitney test]. (ii) INTO delivery of C21 (1.5 ug/kg) either in naïve rats (n=7), or in rats post-stroke (n=4), did not significantly alter baseline blood pressure, heart rate and locomotor activity. Conclusions: Our results demonstrate, that INTO delivery of C21 exerts protective effects after ischemic stroke. These studies suggest INTO administration as potential future route of application of C21 to stroke patients.

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