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.

scholarly journals Oxidative stress-induced renal angiotensin AT1 receptor upregulation causes increased stimulation of sodium transporters and hypertension

2008 ◽  
Vol 295 (3) ◽  
pp. F698-F706 ◽  
Author(s):  
Anees Ahmad Banday ◽  
Mustafa F. Lokhandwala
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Angiotensin Ii ◽  
Map Kinase ◽  
At1 Receptor ◽  
Receptor Expression ◽  
Receptor Protein ◽  
Receptor Signaling ◽  
Sodium Transporters ◽  
Receptor Upregulation

Reactive oxygen species have emerged as important molecules in cardiovascular dysfunction such as diabetes and hypertension. Recent work has shown that oxidative stress and angiotensin II signaling mutually regulate each other by multiple mechanisms and contribute to the development of hypertension. Most of the known biological actions of angiotensin II can be attributed to AT1 receptors. The present study was carried out to investigate the role of renal AT1 receptor signaling in oxidative stress-mediated hypertension. Male Sprague-Dawley rats received tap water (control) or 30 mM l-buthionine sulfoximine (BSO), an oxidant, with and without 1 mM tempol (an antioxidant) for 2 wk. Compared with control rats, BSO-treated rats exhibited increased oxidative stress and reduced antioxidant levels and developed hypertension. BSO treatment also caused increased renal proximal tubular AT1 receptor protein abundance, message levels, and ligand binding. In these rats, angiotensin II caused significantly higher accumulation of inositol trisphosphate (IP3) and phospholipase C (PLC) activation which was sensitive to blockade by AT1 but not to AT2 antagonist. Also, angiotensin II-mediated, AT1-dependent MAP kinase, Na-K-ATPase, and Na/H exchanger 3 activation was higher in BSO-treated rats than in control rats. Tempol supplementation of BSO-treated rats restored redox status, normalized AT1 receptor expression, and decreased blood pressure. Tempol also normalized the angiotensin II-mediated, AT1-dependent IP3 accumulation and PLC, MAP kinase, Na-K-ATPase, and Na/H exchanger 3 stimulation. These data suggest that oxidative stress leads to AT1 receptor upregulation, which in turn causes overstimulation of sodium transporters and subsequently contributes to sodium retention and hypertension. Tempol, while reducing oxidative stress, normalizes AT1 receptor signaling and decreases blood pressure.

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.

Changes in angiotensin type 1 receptor binding and angiotensin-induced pressor responses in the rostral ventrolateral medulla of angiotensinogen knockout mice

2010 ◽  
Vol 298 (2) ◽  
pp. R411-R418 ◽  
Author(s):  
Daian Chen ◽  
Lisa Hazelwood ◽  
Lesley L. Walker ◽  
Brian J. Oldfield ◽  
Michael J. McKinley ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Receptor Binding ◽  
Knockout Mice ◽  
Pressor Response ◽  
Ventrolateral Medulla ◽  
Ang Ii ◽  
Wild Type ◽  
Intravenous Injections ◽  
Angiotensin Type

ANG II, the main circulating effector hormone of the renin-angiotensin system, is produced by enzymatic cleavage of angiotensinogen. The present study aimed to examine whether targeted deletion of the angiotensinogen gene ( Agt) altered brain ANG II receptor density or responsiveness to ANG II. In vitro autoradiography was used to examine the distribution and density of angiotensin type 1 (AT1) and type 2 receptors. In most brain regions, the distribution and density of angiotensin receptors were similar in brains of Agt knockout mice ( Agt −/− ) and wild-type mice. In Agt −/− mice, a small increase in AT1 receptor binding was observed in the rostral ventrolateral medulla (RVLM), a region that plays a critical role in blood pressure regulation. To examine whether Agt −/− mice showed altered responses to ANG II, blood pressure responses to intravenous injection (0.01–0.1 μg/kg) or RVLM microinjection (50 pmol in 50 nl) of ANG II were recorded in anesthetized Agt −/− and wild-type mice. Intravenous injections of phenylephrine (4 μg/kg and 2 μg/kg) were also made in both groups. The magnitude of the pressor response to intravenous injections of ANG II or phenylephrine was not different between Agt −/− and wild-type mice. Microinjection of ANG II into the RVLM induced a pressor response, which was significantly smaller in Agt −/− compared with wild-type mice (+10 ± 1 vs. +23 ± 4 mmHg, respectively, P = 0.004). Microinjection of glutamate into the RVLM (100 pmol in 10 nl) produced a robust pressor response, which was not different between Agt −/− and wild-type mice. A diminished response to ANG II microinjection in the RVLM of Agt −/− mice, despite an increased density of AT1 receptors suggests that signal transduction pathways may be altered in RVLM neurons of Agt −/− mice, resulting in attenuated cellular excitation.

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.

scholarly journals SO031ANGIOTENSIN II TYPE 1 RECEPTOR (AT1R) EXPRESSION IN RENAL TRANSPLANT BIOPSIES AND ANTI-AT1R ANTIBODIES IN SERUM AS AN INDICATOR OF THE RISK OF TRANSPLANT LOSS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Agnieszka Sas-Strózik ◽  
Piotr Donizy ◽  
Katarzyna Kościelska-Kasprzak ◽  
Dorota Kamińska ◽  
Kamila Gawlik ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Graft Loss ◽  
At1 Receptor ◽  
Receptor Expression ◽  
Positive Staining ◽  
Antibody Mediated Rejection ◽  
Peritubular Capillaries ◽  
One Year ◽  
Transplant Biopsy

Abstract Background and Aims The manifestation of anti-angiotensin II type 1 receptor (AT1R) antibodies is considered a risk factor for transplant injury, however, the occurrence of AT1-Receptor expression in renal transplant biopsy may be an additional feature which can help to predict transplant loss. The aim of our study was to evaluate the expression of AT1R together with their antibodies and assess the risk of transplant loss in patients who had a renal transplant indication biopsy. Method AT1-Receptor immunoreactivity was analyzed in renal transplant biopsies. Additionally, we analyzed the presence of anti-AT1R antibodies in these patients using ELISA method. The result of more than 10 was assessed as positive. Immunohistochemical evaluation of AT1-Receptor expression was performed on 4 μm-thick paraffin sections mounted on silanized slides. AT1-Receptor expression was analyzed in five compartments: 1.tubular epithelium, 2.glomeruli, 3.peritubular capillaries, 4.interstitium and 5.renal blood vessels (small and intermediate arteries) based on a 3-step scale. Results We checked 156 samples of biopsies for the immunoreactivity of the AT1-Receptor. In all these patients we were able to access the presence of anti-AT1R antibodies. A group of 67 patients had positive AT1-Receptor expression (R+) and 16 patients had positive anti-AT1R antibodies (R+Ab+) results. A group of 89 patients had no expression of AT1-Receptor (R-), among which 51 had also no anti-AT1R (R-Ab-). One-year post-biopsy graft loss in the R+Ab+ patients was 37% (6/16) compared to 10% (7/69) in the R-Ab- patients (p = 0.006). Two-year and three-year graft loss was 43% vs. 17% (p=0.02) and 50% vs. 21% (p=0.02) respectively. Moreover, six patients had positive staining of AT1-Receptors in microcirculation (glomeruli and peritubular capillaries), which was associated with antibody mediated rejection. Conclusion The presence of anti-AT1R antibodies in serum together with the expression of AT1-Receptor in transplant biopsy was associated with a significantly higher graft loss. The relevance of AT1-Receptor expression analyzed together with anti-AT1R antibodies should be considered for better transplant immunological risk assessment.

Parathyroid hormone/parathyroid hormone-related protein receptor expression in nude mice with a transplantable canine apocrine adenocarcinoma (CAC-8) and humoral hypercalcaemia of malignancy

1997 ◽  
Vol 153 (1) ◽  
pp. 123-129 ◽  
Author(s):  
A Gröne ◽  
L K McCauley ◽  
C C Capen ◽  
T J Rosol
Keyword(s):  
Parathyroid Hormone ◽  
Nude Mice ◽  
Elevated Serum ◽  
Receptor Expression ◽  
Receptor Protein ◽  
Receptor Mrna ◽  
Tumour Bearing ◽  
Parathyroid Hormone Related Protein ◽  
Significant Difference ◽  
Pthrp Receptor

Abstract The effect of humoral hypercalcaemia of malignancy (HHM) on parathyroid hormone/parathyroid hormonerelated protein (PTH/PTHrP) receptor expression was investigated in nude mice with subcutaneous transplantation of an adenocarcinoma line (CAC-8) which produces PTHrP. Serum calcium and PTHrP concentrations were analysed by colorimetric assay and a two-site IRMA respectively. Mice were hypercalcaemic (3·3 ±0·1 mmol/l) compared with non-tumour-bearing control mice (2·1 ± 0·1 mmol/l) and had elevated serum PTHrP concentrations (30·4 ±3·4 pmol/l) compared with non-tumour-bearing control mice (0·7 ±0·1 pmol/l. Lumbar vertebrae were analysed by histomorphometry. Tumourbearing mice had a significant (P<0·01) increase in resorptive perimeter, increased numbers of osteoclasts/mm endosteum and increased endosteal bone-forming perimeter. Total RNA was isolated from calvarium, humerus and kidney and analysed for PTH/PTHrP receptor expression by Northern blot analysis. There was no significant difference between PTH/PTHrP receptor mRNA expression in the kidneys and humeri of tumourbearing mice compared with non-tumour control mice, but a significant increase in PTH/PTHrP receptor expression in calvaria. Kidneys and vertebral bodies were stained for PTH/PTHrP receptor protein by immunohistochemistry. Renal proximal tubules (especially the basolateral regions) and endosteal osteoblasts of control and tumourbearing mice stained positive for PTH/PTHrP receptor. These results demonstrated that HHM induced by increased serum PTHrP concentrations did not result in down-regulation of PTH/PTHrP receptor mRNA or protein expression in vivo. Journal of Endocrinology (1997) 153, 123–129

scholarly journals Regulation of central angiotensin type 1 receptors and sympathetic outflow in heart failure

2009 ◽  
Vol 297 (5) ◽  
pp. H1557-H1566 ◽  
Author(s):  
Irving H. Zucker ◽  
Harold D. Schultz ◽  
Kaushik P. Patel ◽  
Wei Wang ◽  
Lie Gao
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Transcription Factor ◽  
Critical Role ◽  
Good Evidence ◽  
Receptor Expression ◽  
Ventrolateral Medulla ◽  
Sympathetic Outflow ◽  
Angiotensin Type

Angiotensin type 1 receptors (AT1Rs) play a critical role in a variety of physiological functions and pathophysiological states. They have been strongly implicated in the modulation of sympathetic outflow in the brain. An understanding of the mechanisms by which AT1Rs are regulated in a variety of disease states that are characterized by sympathoexcitation is pivotal in development of new strategies for the treatment of these disorders. This review concentrates on several aspects of AT1R regulation in the setting of chronic heart failure (CHF). There is now good evidence that AT1R expression in neurons is mediated by activation of the transcription factor activator protein 1 (AP-1). This transcription factor and its component proteins are upregulated in the rostral ventrolateral medulla of animals with CHF. Because the increase in AT1R expression and transcription factor activation can be blocked by the AT1R antagonist losartan, a positive feedback mechanism of AT1R expression in CHF is suggested. Oxidative stress has also been implicated in the regulation of receptor expression. Recent data suggest that the newly discovered catabolic enzyme angiotensin-converting enzyme 2 (ACE2) may play a role in the modulation of AT1R expression by altering the balance between the octapeptide ANG II and ANG- (1–7). Finally, exercise training reduces both central oxidative stress and AT1R expression in animals with CHF. These data strongly suggest that multiple central and peripheral influences dynamically alter AT1R expression in CHF.

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