scholarly journals Elevated blood pressure in normotensive rats produced by ‘knockdown’ of the angiotensin type 2 receptor

2004 ◽  
Vol 89 (3) ◽  
pp. 313-322 ◽  
Author(s):  
HongWei Wang ◽  
Stefan Gallinat ◽  
Hong-wei Li ◽  
Colin Sumners ◽  
Mohan K. Raizada ◽  
...  
Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Peng Xu ◽  
Kwabena Sarpong ◽  
John J Gildea ◽  
Stephen Marshall ◽  
Wei Yue ◽  
...  

Renal proximal tubule (RPT) dopamine D 1 -like receptors (D 1 R) and angiotensin II type-2 receptor (AT 2 R) inhibit sodium reabsorption and counter regulate the renin angiotensin systems AT 1 R which stimulates sodium reabsorption. Salt sensitivity of blood pressure (SS) is defined as a ≥7-mmHg rise in blood pressure following a week of daily consumption of 350 mM sodium chloride (NaCl). Inverse salt sensitivity (ISS) is defined as a ≥7-mm Hg increase in blood pressure (BP) after a week of 10 mM NaCl/day. Salt resistant controls were defined as < 7mM Hg change in BP whether on 10 or 350mmHg NaCl/day for one week. Previously, we demonstrated that D 1 R RPT membrane recruitment was inversely proportional to an individual’s degree of BP increase on a 350 mM diet. We hypothesize that the degree of salt sensitivity of blood pressure would be inversely correlated with the recruitment of the AT 2 R to the plasma membrane induced by NaCl. Immunostaining shows that D 1 R was distributed in a fine granular manner throughout the whole plasma membrane, while AT 2 R shows a punctate pattern in both urine-derived SR and ISS RPTCs. There was no difference of basal D 1 R or AT 2 R expression. Increasing cell NaCl (monensin ionophore 10 μM, 1 hour) resulted in a significantly more AT 2 R and D 1 R(control) recruitment to cell surface in ISS cells than in SR cells (D 1 R: MON/VEH: SR, 1.032 ± 0.056, n=4; ISS, 1.537 ± 0.097, n=4; t-test, p<0.01; AT 2 R :MON/VEH: SR, 0.923 ± 0.063, n=3; ISS, 1.28 ± 0.106, n=3; t-test, p<0.05). Because ISS individuals present to the medical system with elevated blood pressure while on a low salt diet, they are often misdiagnosed as hypertensive. As our studies were conducted on RPT cells isolated from individual's urine, the D 1 R and AT 2 R response may contribute to the diagnosis of ISS individuals with elevated blood pressure while on a 10 mM salt diet, and provide better understanding on the etiology of ISS.


Author(s):  
Jay S Mishra ◽  
Sathish Kumar

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.


Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Annette D de Kloet ◽  
Lei Wang ◽  
Jacob A Ludin ◽  
Helmut Hiller ◽  
Justin A Smith ◽  
...  

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.


Hypertension ◽  
2001 ◽  
Vol 37 (5) ◽  
pp. 1285-1291 ◽  
Author(s):  
Allan F. Moore ◽  
Nicolas T. Heiderstadt ◽  
Esther Huang ◽  
Nancy L. Howell ◽  
Zhi-Qin Wang ◽  
...  

2006 ◽  
Vol 59 (1-2) ◽  
pp. 67-71
Author(s):  
Aniko Katona-Djurekovic ◽  
Edita Stokic

Introduction. Current clinical practice requires simple and available tools for cardiovascular risk assessment in diabetic patients. Material and methods. This study included 290 type 2 diabetics of both sexes. The following anthropometric parameters were measured: body mass index, waist circumference, sagital abdominal diameter, while ensuing parameters included: waist-to-stature ratio(WSH), ratio of abdominal sagital diameter to height (SADE), and conicity index. Metabolic status was evaluated based on lipidograms and HbAlc, and of cardiovascular parameters blood pressure was measured. Results. Female patients were obese, with central accumulation of fat, elevated blood pressure and lipid disorders such as hypo-HDL cholesterolemia. The applied anthropometric parameters and indicators ensuing from them (WSH, SADH and conicity index), are reliable indicators of elevated blood pressure in diabetic patients. Conclusion. The obtained results showed negative correlation with HDL cholesterol in women, which indirectly indicates to development of hypertension, as one of the most common diabetic complications. Central accumulation of fat with dyslipidemic disorder, characteristic of metabolic syndrome, is of highest importance. Sagital abdominal diameter (SAD) and WSH showed the highest correlation with lipidograms in females, whereas BMI was the best indicator in males. .


Endocrinology ◽  
2008 ◽  
Vol 150 (3) ◽  
pp. 1421-1428 ◽  
Author(s):  
Laurent Yvan-Charvet ◽  
Florence Massiéra ◽  
Noël Lamandé ◽  
Gérard Ailhaud ◽  
Michèle Teboul ◽  
...  

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.


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