scholarly journals The Receptor AT1 Appears to Be Important for the Maintenance of Bone Mass and AT2 Receptor Function in Periodontal Bone Loss Appears to Be Regulated by AT1 Receptor

2021 ◽  
Vol 22 (23) ◽  
pp. 12849
Author(s):  
Maria Laura de Souza Lima ◽  
Agnes Andrade Martins ◽  
Caroline Addison Carvalho Xavier de Medeiros ◽  
Gerlane Coelho Bernardo Guerra ◽  
Robson Santos ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Mass ◽  
Alveolar Bone ◽  
Experimental Studies ◽  
At1 Receptor ◽  
At2 Receptor ◽  
Ang Ii ◽  
Key Events

A large number of experimental studies has demonstrated that angiotensin II (Ang II) is involved in key events of the inflammatory process. This study aimed to evaluate the role of Ang II type 1 (AT1) and Ang II type 2 (AT2) receptors on periodontitis. Methods: Experimental periodontitis was induced by placing a 5.0 nylon thread ligature around the second upper left molar of AT1 mice, no-ligature or ligature (AT1-NL and AT1-L), AT2 (AT2-NL or AT2-L) and wild type (WT-NL or L). Alveolar bone loss was scanned using Micro-CT. Cytokines, peptides and enzymes were analyzed from gingival tissues by Elisa and RT-PCR. Results: The blockade of AT1 receptor resulted in bone loss, even in healthy animals. Ang II receptor blockades did not prevent linear bone loss. Ang II and Ang 1-7 levels were significantly increased in the AT2-L (p < 0.01) group compared to AT2-NL and AT1-L. The genic expression of the Mas receptor was significantly increased in WT-L and AT2-L compared to (WT-NL and AT2-NL, respectively) and in AT1-L. Conclusions: Our data suggest that the receptor AT1 appears to be important for the maintenance of bone mass. AT2 receptor molecular function in periodontitis appears to be regulated by AT1.

Abstract P284: Angiotensin II Upregulates Cytochrome-450 4A Expression in Rat Kidney Through Type 1 Receptor

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Wanting Wang ◽  
Rong Rong ◽  
Osamu Ito ◽  
Yoshiko Ogawa ◽  
Yoshikazu Muroya ◽  
...  
Keyword(s):  
Renal Cortex ◽  
Urinary Albumin Excretion ◽  
Rat Kidney ◽  
At1 Receptor ◽  
Urinary Albumin ◽  
High Dose ◽  
At2 Receptor ◽  
Ang Ii ◽  
Outer Medulla

20-hydroxyeicosatetraenoic acids (20-HETE) is a cytochrome P-450 (CYP) 4A-dependent metabolite of arachidonic acid and regulates vascular tone and renal tubular function. Previous studies showed that angiotensin II (Ang II) stimulated the renal CYP activity and 20-HETE production through the Ang II type 1 (AT1) receptor and that the Ang II-increased the 20-HETE was linked to the Ang II type 2(AT2) receptor. Thus, the study was designed to clarify the role of Ang II in CYP4A isoforms expression in the rat kidney. Male Sprague-Dawley rats were infused Ang II at low dose (AL, 0.17mg/kg/min, sc) and high dose (AH, 0.70mg/kg/day, sc) by using osmotic mini pump, with or without AT1 receptor blocker candesartan (1 and 3mg/kg/day, po) for 1 week. The protein expression of CYP4A isoforms, AT1 receptor and AT2 receptor in the renal cortex, outer medulla, and inner medulla was examined by immunoblot analysis. The mRNA expression of CYP4A isoforms was examined by reverse transcription and polymerase chain reaction (RT-PCR). Ang II at high dose increased systolic blood pressure (control, 109±2; AH, 164±8 mmHg, p<0.01), creatinine (control, 0.24±0.00; AH, 0.29±0.01 mg/dl, p<0.01) and urinary albumin excretion (control, 20.3±5.9; AH, 2398.6±303.6 μg/mg creatinine, p<0.01). In the control group, the CYP4A1, 4A2, and 4A8 proteins were highly expressed in the renal cortex, lowly expressed in the outer medulla, barely detected in the inner medulla. The AT1 receptor was expressed in kidney sections; highly in the outer and inner medulla, the AT2 receptor was only detected in the outer medulla. Ang II dose-dependently increased all CYP4A isoform proteins in the renal cortex and outer medulla (CYP4A1, 24% and 222%; CYP4A2, by 51% and 258%; CYP4A8, by 52% and 550%, p<0.05). Ang II also increased all CYP4A isoform mRNAs in the renal cortex and outer medulla. The candesartan treatment dose-dependently inhibited the Ang II-increased blood pressure, creatinine, urinary albumin excretion and CYP4A isoform expressions. These results indicated that Ang II increases CYP4A isoform expressions in the kidney through AT1 receptor. The Ang II-upregulated CYP4A expressions may play an important role in hypertension and renal function.

Central angiotensin II AT1 receptors mediate fetal swallowing and pressor responses in the near-term ovine fetus

2005 ◽  
Vol 288 (4) ◽  
pp. R1014-R1020 ◽  
Author(s):  
Mostafa A. El-Haddad ◽  
Yaser Ismail ◽  
Dave Gayle ◽  
Michael G. Ross
Keyword(s):  
At1 Receptor ◽  
Receptor Blocker ◽  
At2 Receptor ◽  
Ang Ii ◽  
At1 Receptors ◽  
Pressor Responses ◽  
Ovine Fetus ◽  
Near Term ◽  
At2 Receptors

Swallowed volumes in the fetus are greater than adult values (per body weight) and serve to regulate amniotic fluid volume. Central ANG II stimulates swallowing, and nonspecific ANG II receptor antagonists inhibit both spontaneous and ANG II-stimulated swallowing. In the adult rat, AT1 receptors mediate both stimulated drinking and pressor activities, while the role of AT2 receptors is controversial. As fetal brain contains increased ANG II receptors compared with the adult brain, we sought to investigate the role of both AT1 and AT2 receptors in mediating fetal swallowing and pressor activities. Five pregnant ewes with singleton fetuses (130 ± 1 days) were prepared with fetal vascular and lateral ventricle (LV) catheters and electrocorticogram and esophageal electromyogram electrodes and received three studies over 5 days. On day 1 (ANG II), following a 2-h basal period, 1 ml artificial cerebrospinal fluid (aCSF) was injected in the LV. At time 4 h, ANG II (6.4 μg) was injected in the LV, and the fetus was monitored for a final 2 h. On day 3, AT1 receptor blocker (losartan 0.5 mg) was administered at 2 h, and ANG II plus losartan was administered at 4 h. On day 5, AT2 receptor blocker (PD-123319; 0.8mg) was administered at 2 h and ANG II plus PD-123319 at 4 h. In the ANG II study, LV injection of ANG II significantly increased fetal swallowing (0.9 ± 0.1 to 1.4 ± 0.1 swallows/min; P < 0.05). In the losartan study, basal fetal swallowing significantly decreased in response to blockade of AT1 receptors (0.9 ± 0.1 to 0.4 ± 0.1 swallows/min; P < 0.05), while central injection of ANG II in the presence of AT1 receptor antagonism did not increase fetal swallowing (0.6 ± 0.1 swallows/min). In the PD-123319 study, basal fetal swallowing did not change in response to blockade of AT2 receptor (0.9 ± 0.1 swallows/min), while central injection of ANG II in the presence of AT2 blockade significantly increased fetal swallowing (1.5 ± 0.1 swallows/min; P < 0.05). ANG II caused significant pressor responses in the control and PD-123319 studies but no pressor response in the presence of AT1 blockade. These data demonstrate that in the near-term ovine fetus, AT1 receptor but not AT2 receptors accessible via CSF contribute to dipsogenic and pressor responses.

ACE2/Angiotensin-(1-7)/Mas Receptor Axis in Human Cancer: Potential Role for Pediatric Tumors

2020 ◽  
Vol 21 (9) ◽  
pp. 892-901 ◽  
Author(s):  
Ana Luiza Ataide Carneiro de Paula Gonzaga ◽  
Vitória Andrade Palmeira ◽  
Thomas Felipe Silva Ribeiro ◽  
Larissa Braga Costa ◽  
Karla Emília de Sá Rodrigues ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Angiotensin Ii ◽  
Pediatric Cancer ◽  
Pediatric Patients ◽  
Human Cancer ◽  
Experimental Studies ◽  
At1 Receptor ◽  
Pediatric Tumors ◽  
Mas Receptor

Background: Pediatric tumors remain the highest cause of death in developed countries. Research on novel therapeutic strategies with lesser side effects is of utmost importance. In this scenario, the role of Renin-Angiotensin System (RAS) axes, the classical one formed by angiotensinconverting enzyme (ACE), Angiotensin II and AT1 receptor and the alternative axis composed by ACE2, Angiotensin-(1-7) and Mas receptor, have been investigated in cancer. Objective: This review aimed to summarize the pathophysiological role of RAS in cancer, evidence for anti-tumor effects of ACE2/Angiotensin-(1-7)/Mas receptor axis and future therapeutic perspectives for pediatric cancer. Methods: Pubmed, Scopus and Scielo were searched in regard to RAS molecules in human cancer and pediatric patients. The search terms were “RAS”, “ACE”, “Angiotensin-(1-7)”, “ACE2”, “Angiotensin II”, “AT1 receptor”, “Mas receptor”, “Pediatric”, “Cancer”. Results: Experimental studies have shown that Angiotensin-(1-7) inhibits the growth of tumor cells and reduces local inflammation and angiogenesis in several types of cancer. Clinical trials with Angiotensin-( 1-7) or TXA127, a pharmaceutical grade formulation of the naturally occurring peptide, have reported promising findings, but not enough to recommend medical use in human cancer. In regard to pediatric cancer, only three articles that marginally investigated RAS components were found and none of them evaluated molecules of the alternative RAS axis. Conclusion: Despite the potential applicability of Angiotensin-(1-7) in pediatric tumors, the role of this molecule was never tested. Further clinical trials are necessary, also including pediatric patients, to confirm safety and efficiency and to define therapeutic targets.

scholarly journals AT1 and AT2 Receptor Knockout Changed Osteonectin and Bone Density in Mice in Periodontal Inflammation Experimental Model

2021 ◽  
Vol 22 (10) ◽  
pp. 5217
Author(s):  
Maria Laura de Souza Lima ◽  
Caroline Addison Carvalho Xavier de Medeiros ◽  
Gerlane Coelho Bernardo Guerra ◽  
Robson Santos ◽  
Michael Bader ◽  
...  
Keyword(s):  
Bone Density ◽  
Bone Loss ◽  
Experimental Model ◽  
At2 Receptor ◽  
Micro Ct ◽  
Rt Pcr ◽  
Osteoblast Cells ◽  
Periodontal Inflammation ◽  
Bone Trabeculae

Background: The aim of this study was to evaluate the role of AT1 and AT2 receptors in a periodontal inflammation experimental model. Methods: Periodontal inflammation was induced by LPS/Porphyromonas gingivalis. Maxillae, femur, and vertebra were scanned using Micro-CT. Maxillae were analyzed histopathologically, immunohistochemically, and by RT-PCR. Results: The vertebra showed decreased BMD in AT1 H compared with WT H (p < 0.05). The femur showed increased Tb.Sp for AT1 H and AT2 H, p < 0.01 and p < 0.05, respectively. The Tb.N was decreased in the vertebra (WT H-AT1 H: p < 0.05; WT H-AT2 H: p < 0.05) and in the femur (WT H-AT1 H: p < 0.01; WT H-AT2 H: p < 0.05). AT1 PD increased linear bone loss (p < 0.05) and decreased osteoblast cells (p < 0.05). RANKL immunostaining was intense for AT1 PD and WT PD (p < 0.001). OPG was intense in the WT H, WT PD, and AT2 PD when compared to AT1 PD (p < 0.001). AT1 PD showed weak immunostaining for osteocalcin compared with WT H, WT PD, and AT2 PD (p < 0.001). AT1 H showed significantly stronger immunostaining for osteonectin in fibroblasts compared to AT2 H (p < 0.01). Conclusion: AT1 receptor knockout changed bone density, the quality and number of bone trabeculae, decreased the number of osteoblast cells, and increased osteonectin in fibroblasts.

Reactive Oxygen Species-Mediated Homologous Downregulation of Angiotensin II Type 1 Receptor Mrna by Angiotensin II

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 688-688
Author(s):  
Toshihiro Ichiki ◽  
Kotaro Takeda ◽  
Akira Takeshita
Keyword(s):  
Reactive Oxygen Species ◽  
Angiotensin Ii ◽  
Nadph Oxidase ◽  
Mrna Expression ◽  
Crucial Role ◽  
Oxygen Species ◽  
Ang Ii ◽  
Stimulation Of

58 Recent studies suggest a crucial role of reactive oxygen species (ROS) for the signaling of Angiotensin II (Ang II) through type 1 Ang II receptor (AT1-R). However, the role of ROS in the regulation of AT1-R expression has not been explored. In this study, we examined the effect of an antioxidant on the homologous downregulation of AT1-R by Ang II. Ang II (10 -6 mol/L) decreased AT1-R mRNA with a peak suppression at 6 hours of stimulation in rat aortic vascular smooth muscle cells (VSMC). Ang II dose-dependently (10 -8 -10 -6 ) suppressed AT1-R mRNA at 6 hours of stimulation. Preincubation of VSMC with N-acetylcysteine (NAC), a potent antioxidant, almost completely inhibited the Ang II-induced downregulation of AT1-R mRNA. The effect of NAC was due to stabilization of the AT1-R mRNA that was destabilized by Ang II. Ang II did not affect the promoter activity of AT1-R gene. Diphenylene iodonium (DPI), an inhibitor of NADH/NADPH oxidase failed to inhibit the Ang II-induced AT1-R mRNA downregulation. The Ang II-induced AT1-R mRNA downregulation was also blocked by PD98059, an extracellular signal-regulated protein kinase (ERK) kinase inhibitor. Ang II-induced ERK activation was inhibited by NAC as well as PD98059 whereas DPI did not inhibit it. To confirm the role of ROS in the regulation of AT1-R mRNA expression, VSMC were stimulated with H 2 O 2 . H 2 O 2 suppressed the AT1-R mRNA expression and activated ERK. These results suggest that production of ROS and activation of ERK are critical for downregulation of AT1-R mRNA. The differential effect of NAC and DPI on the downregulation of AT1-R mRNA may suggest the presence of other sources than NADH/NADPH oxidase pathway for ROS in Ang II signaling. Generation of ROS through stimulation of AT1-R not only mediates signaling of Ang II but may play a crucial role in the adaptation process of AT1-R to the sustained stimulation of Ang II.

Abstract P059: A A Role of Aminopeptidase A in the Brain on Cardiovascular Regulation of Conscious Rat

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Takuto Nakamura ◽  
Masanobu Yamazato ◽  
Akio Ishida ◽  
Yusuke Ohya
Keyword(s):  
Blood Pressure ◽  
Protein Expression ◽  
Drinking Behavior ◽  
Cardiovascular Regulation ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Aminopeptidase A ◽  
The Brain

Objective: Aminopeptidase A (APA) have important role in conversion of Ang II to Ang III. Intravenous APA administration lowers blood pressure in hypertensive rats. In contrast, APA inhibition in the brain lowers blood pressure in hypertensive rats. Therefore APA might have different role on cardiovascular regulation. However, a role of APA and Ang III on cardiovascular regulation especially in the brain has not been fully understood. Our purpose of present study was to investigate a role of APA and Ang III in the brain on cardiovascular regulation in conscious state. Method: 12-13 weeks old Wistar Kyoto rat (WKY) and 12-16 weeks old spontaneously hypertensive rat (SHR) were used. i) APA distribution in the brain was evaluated by immunohistochemistry. Protein expression of APA was evaluated by Western blotting. Enzymatic activity of APA was evaluated using L-glutamic acid γ-(4-nitroanilide) as a substrate. ii) WKY received icv administration of Ang II 25ng/2μL and Ang III 25ng/2μL. We recorded change in mean arterial pressure (MAP) in conscious and unrestraied state and measured induced drinking time. iii) SHR received icv administeration of recombinant APA 400ng/4μL. We recorded change in MAP in conscious and unrestraied state and measured induced drinking time. Result: i) APA was diffusely immunostained in the cells of brain stem including cardiovascular regulatory area such as rostral ventrolateral medulla. Protein expression and APA activity in the brain were similar between WKY (n=3) and SHR (n=3).ii) Icv administration of Ang II increased MAP by 33.8±3.8 mmHg and induced drinking behavior for 405±90 seconds (n=4). Icv administration of Ang III also increased MAP by 24.7±2.4 mmHg and induced drinking behavior for 258±62 seconds (n=3). These vasopressor activity and induced drinking behavior was completely blocked by pretretment of angiotensin receptor type 1 blocker.iii) Icv administration of APA increased MAP by 10.0±1.7 mmHg (n=3). Conclusion: These results suggested that Ang III in the brain increase blood pressure by Angiotensin type 1 receptor dependent mechanism and APA in the brain may involved in blood pressure regulation as a vasopressor enzyme.

Endogenous ANG II supports lumbar sympathetic activity in conscious sodium-deprived rats: role of area postrema

1998 ◽  
Vol 275 (1) ◽  
pp. R46-R55 ◽  
Author(s):  
Ling Xu ◽  
John P. Collister ◽  
John W. Osborn ◽  
Virginia L. Brooks
Keyword(s):  
Sympathetic Activity ◽  
Food Restriction ◽  
Sympathetic Nerve Activity ◽  
Area Postrema ◽  
Ang Ii ◽  
Nerve Activity ◽  
Baroreflex Control ◽  
Maximal Gain

This study tests the hypothesis that the area postrema (AP) is necessary for endogenous ANG II to chronically maintain lumbar sympathetic nerve activity (LSNA) and heart rate (HR) in conscious sodium-deprived rats. The effect of the ANG II type 1-receptor antagonist, losartan, on LSNA and HR was determined in rats that were either AP lesioned (APX) or sham lesioned. The sham rats were divided into groups, with (SFR) or without (SAL) food restriction, to control for the decreased food intake of APX rats. Before losartan, basal mean arterial pressure (MAP), HR, and baroreflex control of LSNA and HR were similar between groups, with the exception of lower maximal reflex LSNA and higher maximal gain of the HR-MAP curve in APX rats. In all groups, losartan similarly shifted ( P < 0.01) the LSNA-MAP curve to the left without altering maximal gain. Losartan also decreased ( P < 0.05) minimal LSNA in all groups, and suppressed ( P < 0.01) maximal LSNA (% of control) in SFR (240 ± 13 to 205 ± 15) and SAL (231 ± 21 to 197 ± 26) but not APX (193 ± 10 to 185 ± 8) rats. In general, losartan similarly shifted the HR-MAP curve to a lower MAP in all groups. The results suggest that the AP is not necessary for endogenous ANG II to chronically support LSNA and HR at basal and elevated MAP levels in sodium-deprived rats. However, the AP is required for endogenous ANG II to increase maximal reflex LSNA at low MAP levels.

Exposure to environmental chemicals and type 1 diabetes: an update

2019 ◽  
Vol 73 (6) ◽  
pp. 483-488 ◽  
Author(s):  
Sarah G Howard
Keyword(s):  
Type 1 Diabetes ◽  
Experimental Studies ◽  
Epidemiological Studies ◽  
Environmental Chemicals ◽  
Exposure Level ◽  
Environmental Chemical ◽  
Timing Of Exposure

This narrative review summarises recently published epidemiological and in vivo experimental studies on exposure to environmental chemicals and their potential role in the development of type 1 diabetes mellitus (T1DM). These studies focus on a variety of environmental chemical exposures, including to air pollution, arsenic, some persistent organic pollutants, pesticides, bisphenol A and phthalates. Of the 15 epidemiological studies identified, 14 include measurements of exposures during childhood, 2 include prenatal exposures and 1 includes adults over age 21. Together, they illustrate that the role of chemicals in T1DM may be complex and may depend on a variety of factors, such as exposure level, timing of exposure, nutritional status and chemical metabolism. While the evidence that these exposures may increase the risk of T1DM is still preliminary, it is critical to investigate this possibility further as a means of preventing T1DM.

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.

Localization of angiotensin II type 1 receptor subtype mRNA in rat kidney

1995 ◽  
Vol 268 (2) ◽  
pp. F220-F226 ◽  
Author(s):  
D. P. Healy ◽  
M. Q. Ye ◽  
M. Troyanovskaya
Keyword(s):  
In Situ Hybridization ◽  
Rat Kidney ◽  
At1 Receptor ◽  
Receptor Subtypes ◽  
Mrna Levels ◽  
Ang Ii ◽  
Outer Medulla ◽  
Vasa Recta

The physiological effects of angiotensin II (ANG II) on the kidney are mediated primarily by the ANG II type 1 (AT1) receptor. Two highly similar AT1 receptor subtypes have been identified in the rat by molecular cloning techniques, namely AT1A and AT1B. The intrarenal localization of the AT1A and AT1B receptor subtypes has not been studied by hybridization methods with subtype-specific receptor probes. Using radiolabeled probes from the 3' noncoding region of the AT1A and AT1B cDNAs, we localized AT1 mRNA in rat kidney by in situ hybridization. Specificity of the 3' noncoding region probes was tested by Northern blot and solution hybridization methods. AT1A mRNA levels were highest in the liver, kidney, and adrenal. In contrast, AT1B mRNA levels were highest in the adrenal and pituitary and low in kidney. Autoradiographic localization of 125I-[Sar1,Ile8]ANG II binding indicated that the highest levels of AT1 receptors were found in glomeruli and vascular elements. In situ hybridization with a nonselective AT1 receptor riboprobe indicated that the highest levels of AT1 mRNA were in the outer medullary vasa recta and cortical glomeruli with additional diffuse labeling of the cortex and outer medulla, consistent with labeling of tubular elements. In contrast, in situ hybridization with the AT1 subtype selective probes revealed that AT1A receptor mRNA was primarily localized to the vasa recta and diffusely to the outer stripe of the outer medulla and the renal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

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