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  1. Article ; Online: A single dose of angiotensin-(1-7) resolves eosinophilic inflammation and protects the lungs from a secondary inflammatory challenge.

    Magalhaes, Giselle Santos / Gregorio, Juliana Fabiana / Beltrami, Vinicius Amorim / Felix, Franciel Batista / Oliveira-Campos, Livia / Bonilha, Caio Santos / Righetti, Renato Fraga / Tibério, Iolanda de Fátima Lopes Calvo / De Sousa, Frederico B / Rezende, Barbara Maximino / Teixeira-Carvalho, Andréa / Santos, Robson As / Campagnole-Santos, Maria José / Rodrigues-Machado, Maria da Gloria / Teixeira, Mauro Martins / Pinho, Vanessa

    Inflammation research : official journal of the European Histamine Research Society ... [et al.

    2024  Volume 73, Issue 6, Page(s) 1019–1031

    Abstract: Objective: Angiotensin-(1-7) [Ang-(1-7)] is a pro-resolving mediator. It is not known whether the pro-resolving effects of Ang-(1-7) are sustained and protect the lung from a subsequent inflammatory challenge. This study sought to investigate the impact ...

    Abstract Objective: Angiotensin-(1-7) [Ang-(1-7)] is a pro-resolving mediator. It is not known whether the pro-resolving effects of Ang-(1-7) are sustained and protect the lung from a subsequent inflammatory challenge. This study sought to investigate the impact of treatment in face of a second allergic or lipopolysaccharide (LPS) challenge.
    Methods: Mice, sensitized and challenged with ovalbumin (OVA), received a single Ang-(1-7) dose at the peak of eosinophilic inflammation, 24 h after the final OVA challenge. Subsequently, mice were euthanized at 48, 72, 96, and 120 h following the OVA challenge, and cellular infiltrate, inflammatory mediators, lung histopathology, and macrophage-mediated efferocytic activity were evaluated. The secondary inflammatory stimulus (OVA or LPS) was administered 120 h after the last OVA challenge, and subsequent inflammatory analyses were performed.
    Results: Treatment with Ang-(1-7) resulted in elevated levels of IL-10, CD4
    Conclusion: A single dose of Ang-(1-7) resolves lung inflammation and protect the lung from a subsequent inflammatory challenge highlighting its potential therapeutic for individuals with asthma.
    MeSH term(s) Animals ; Angiotensin I/therapeutic use ; Angiotensin I/pharmacology ; Angiotensin I/administration & dosage ; Peptide Fragments/pharmacology ; Peptide Fragments/therapeutic use ; Peptide Fragments/administration & dosage ; Lung/drug effects ; Lung/pathology ; Lung/immunology ; Lipopolysaccharides ; Ovalbumin/immunology ; Mice ; Male ; Macrophages/drug effects ; Macrophages/immunology ; Eosinophils/drug effects ; Eosinophils/immunology ; Mice, Inbred BALB C ; Inflammation/drug therapy ; Eosinophilia/drug therapy ; Eosinophilia/immunology ; Bronchoalveolar Lavage Fluid/immunology ; Bronchoalveolar Lavage Fluid/cytology
    Chemical Substances angiotensin I (1-7)
    Language English
    Publishing date 2024-04-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1221794-3
    ISSN 1420-908X ; 1023-3830
    ISSN (online) 1420-908X
    ISSN 1023-3830
    DOI 10.1007/s00011-024-01880-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Genetic deletion of Mas receptor in FVB/N mice impairs cardiac use of glucose and lipids

    Monteiro, Brenda L. / Santos, Robson A.S. / Mario, Erica G. / Araujo, Thiago S. / Savergnini, Silvia S.Q. / Santiago, Andrezza F. / Muzzi, Ruthnea A.L. / Castro, Isabela C. / Teixeira, Lilian G. / Botion, Leida M. / Marinho, Barbhara M. / Santos, Sergio H.S. / Porto, Laura C.J.

    Peptides. 2022 May, v. 151

    2022  

    Abstract: Angiotensin-(1−7) is a biologically active product of the renin-angiotensin system cascade and exerts inhibitory effects on inflammation, vascular and cellular growth mechanisms signaling through the G protein-coupled Mas receptor. The major purpose of ... ...

    Abstract Angiotensin-(1−7) is a biologically active product of the renin-angiotensin system cascade and exerts inhibitory effects on inflammation, vascular and cellular growth mechanisms signaling through the G protein-coupled Mas receptor. The major purpose of the present study was to investigate the use of glucose and fatty acids by cardiac tissue in Mas knockout mice models. Serum levels of glucose, lipids, and insulin were measured in Mas-deficient and wild-type FVB/N mice. To investigate the cardiac use of lipids, the lipoprotein lipase, the gene expression of peroxisome proliferator-activated receptor alpha; carnitine palmitoyltransferase I and acyl-CoA oxidase were evaluated. To investigate the cardiac use of glucose, the insulin signaling through Akt/GLUT4 pathway, glucose-6-phosphate (G-6-P) and fructose-6-phosphate (F-6-P) glycolytic intermediates, in addition to ATP, lactate and the glycogen content were measured. Despite normal body weight, cholesterol and insulin, Mas-Knockout mice presented hyperglycemia and hypertriglyceridemia, impaired insulin signaling, through reduced phosphorylation of AKT and decreased translocation of GLUT4 in response to insulin, with subsequent decrease of the cardiac G-6-P and F-6-P. Lactate production and glycogen content were not altered in Mas-KO hearts. Mas-KO presented reduced cardiac lipoprotein lipase activity and decreased translocation of CD36 in response to insulin. The expression of peroxisome proliferator-activated receptor alpha and carnitine palmitoyltransferase I genes were lower in Mas-KO animals compared to wild-type animals. The ATP content of Mas-KO hearts was smaller than in wild-type. The present results suggest that genetic deletion of Mas produced a devastating effect on cardiac use of glucose and lipids, leading to lower energy efficiency in the heart.
    Keywords acyl-CoA oxidase ; blood serum ; body weight ; carnitine palmitoyltransferase ; cell growth ; cholesterol ; energy efficiency ; fructose 6-phosphate ; gene expression ; glucose ; glucose 6-phosphate ; glycogen ; glycolysis ; heart ; hyperglycemia ; hypertriglyceridemia ; inflammation ; insulin ; lactic acid ; lipoprotein lipase ; peptides ; peroxisome proliferator-activated receptor alpha ; phosphorylation ; renin-angiotensin system
    Language English
    Dates of publication 2022-05
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 769028-9
    ISSN 1873-5169 ; 0196-9781
    ISSN (online) 1873-5169
    ISSN 0196-9781
    DOI 10.1016/j.peptides.2022.170764
    Database NAL-Catalogue (AGRICOLA)

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  3. Article: Diminazene Aceturate, an angiotensin converting enzyme 2 (ACE2) activator, promotes cardioprotection in ischemia/reperfusion-induced cardiac injury

    Coutinho, Danielle C.O. / Santos-Miranda, Artur / Joviano-Santos, Julliane V. / Foureaux, Giselle / Santos, Anderson / Rodrigues-Ferreira, Clara / Martins-Júnior, Paulo A. / Resende, Rodrigo R. / Medei, Emiliano / Vieyra, Adalberto / Santos, Robson A.S. / Cruz, Jader S. / Ferreira, Anderson J.

    Peptides. 2022 May, v. 151

    2022  

    Abstract: This study aimed to investigate whether the Diminazene Aceturate (DIZE), an angiotensin-converting enzyme 2 (ACE2) activator, can revert cardiac dysfunction in ischemia reperfusion-induced (I/R) injury in animals and examine the mechanism underlying this ...

    Abstract This study aimed to investigate whether the Diminazene Aceturate (DIZE), an angiotensin-converting enzyme 2 (ACE2) activator, can revert cardiac dysfunction in ischemia reperfusion-induced (I/R) injury in animals and examine the mechanism underlying this effect. Wistar rats systemically received DIZE (1 mg/kg) for thirty days. Cardiac function in isolated rat hearts was evaluated using the Langendorff technique. After I/R, ventricular non-I/R and I/R samples were used to evaluate ATP levels. Mitochondrial function was assessed using cardiac permeabilized fibers and isolated cardiac mitochondria. Cardiac cellular electrophysiology was evaluated using the patch clamp technique. DIZE protected the heart after I/R from arrhythmia and cardiac dysfunction by preserving ATP levels, independently of any change in coronary flow and heart rate. DIZE improved mitochondrial function, increasing the capacity for generating ATP and reducing proton leak without changing the specific citrate synthase activity. The activation of the ACE2 remodeled cardiac electrical profiles, shortening the cardiac action potential duration at 90 % repolarization. Additionally, cardiomyocytes from DIZE-treated animals exhibited reduced sensibility to diazoxide (KATP agonist) and a higher KATP current compared to the controls. DIZE was able to improve mitochondrial function and modulate cardiac electrical variables with a cardio-protective profile, resulting in direct myocardial cell protection from I/R injury.
    Keywords action potentials ; agonists ; arrhythmia ; cardiac output ; cardiomyocytes ; cardioprotective effect ; citrate (si)-synthase ; diazoxide ; diminazene ; heart rate ; ischemia ; mitochondria ; peptides ; peptidyl-dipeptidase A ; rats
    Language English
    Dates of publication 2022-05
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 769028-9
    ISSN 1873-5169 ; 0196-9781
    ISSN (online) 1873-5169
    ISSN 0196-9781
    DOI 10.1016/j.peptides.2022.170746
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Angiotensin-(1-7)/MasR axis promotes migration of monocytes/macrophages with a regulatory phenotype to perform phagocytosis and efferocytosis.

    Zaidan, Isabella / Tavares, Luciana P / Sugimoto, Michelle A / Lima, Kátia M / Negreiros-Lima, Graziele L / Teixeira, Lívia Cr / Miranda, Thais C / Valiate, Bruno Vs / Cramer, Allysson / Vago, Juliana Priscila / Campolina-Silva, Gabriel H / Souza, Jéssica Am / Grossi, Laís C / Pinho, Vanessa / Campagnole-Santos, Maria Jose / Santos, Robson As / Teixeira, Mauro M / Galvão, Izabela / Sousa, Lirlândia P

    JCI insight

    2022  Volume 7, Issue 1

    Abstract: Nonphlogistic migration of macrophages contributes to the clearance of pathogens and apoptotic cells, a critical step for the resolution of inflammation and return to homeostasis. Angiotensin-(1-7) [Ang-(1-7)] is a heptapeptide of the renin-angiotensin ... ...

    Abstract Nonphlogistic migration of macrophages contributes to the clearance of pathogens and apoptotic cells, a critical step for the resolution of inflammation and return to homeostasis. Angiotensin-(1-7) [Ang-(1-7)] is a heptapeptide of the renin-angiotensin system that acts through Mas receptor (MasR). Ang-(1-7) has recently emerged as a novel proresolving mediator, yet Ang-(1-7) resolution mechanisms are not fully determined. Herein, Ang-(1-7) stimulated migration of human and murine monocytes/macrophages in a MasR-, CCR2-, and MEK/ERK1/2-dependent manner. Pleural injection of Ang-(1-7) promoted nonphlogistic mononuclear cell influx alongside increased levels of CCL2, IL-10, and macrophage polarization toward a regulatory phenotype. Ang-(1-7) induction of CCL2 and mononuclear cell migration was also dependent on MasR and MEK/ERK. Of note, MasR was upregulated during the resolution phase of inflammation, and its pharmacological inhibition or genetic deficiency impaired mononuclear cell recruitment during self-resolving models of LPS pleurisy and E. coli peritonitis. Inhibition/absence of MasR was associated with reduced CCL2 levels, impaired phagocytosis of bacteria, efferocytosis, and delayed resolution of inflammation. In summary, we have uncovered a potentially novel proresolving feature of Ang-(1-7), namely the recruitment of mononuclear cells favoring efferocytosis, phagocytosis, and resolution of inflammation. Mechanistically, cell migration was dependent on MasR, CCR2, and the MEK/ERK pathway.
    MeSH term(s) Angiotensin I/metabolism ; Angiotensin I/pharmacology ; Animals ; Cells, Cultured ; Disease Models, Animal ; Humans ; Inflammation/metabolism ; MAP Kinase Signaling System/physiology ; Macrophages/drug effects ; Macrophages/physiology ; Male ; Mice ; Mice, Inbred BALB C ; Monocytes/drug effects ; Monocytes/physiology ; Peptide Fragments/metabolism ; Peptide Fragments/pharmacology ; Peritonitis ; Phagocytosis/drug effects ; Phagocytosis/physiology ; Phenotype ; Proto-Oncogene Mas/metabolism ; Receptors, CCR2/metabolism
    Chemical Substances Peptide Fragments ; Proto-Oncogene Mas ; Receptors, CCR2 ; Angiotensin I (9041-90-1) ; angiotensin I (1-7) (IJ3FUK8MOF)
    Language English
    Publishing date 2022-01-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.147819
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Angiotensin II type 2 receptor mediates high fat diet-induced cardiomyocyte hypertrophy and hypercholesterolemia

    Lima, Vanessa M / Bader, Michael / Barreto-Chaves, Maria Luiza M / de Oliveira Silva, Tábatha / Diniz, Gabriela P / Fonseca, Renata I.B / Júnior, Jose Donato / Lino, Caroline A / Santos, Robson A.S / Senger, Nathalia

    Molecular and cellular endocrinology. 2019 Sept. 09,

    2019  

    Abstract: Obesity is the major risk factor for several cardiovascular and metabolic disorders. Previous studies reported that deletion of Angiotensin II type 2 receptor (AT2R) protects against metabolic dysfunctions induced by high fat (HF) diet. However, the role ...

    Abstract Obesity is the major risk factor for several cardiovascular and metabolic disorders. Previous studies reported that deletion of Angiotensin II type 2 receptor (AT2R) protects against metabolic dysfunctions induced by high fat (HF) diet. However, the role of AT2R in obesity-induced cardiac hypertrophy remains unclear. Male AT2R knockout (AT2RKO) and wild type (AT2RWT) mice were fed with control or HF diet for 10 weeks. HF diet increased cardiac expression of AT2R in obese mice. Deletion of AT2R did not affect body weight gain, glucose intolerance and fat mass gain induced by HF feeding. However, loss of AT2R prevented HF diet-induced hypercholesterolemia and cardiac remodeling. Mechanistically, we found that pharmacological inhibition or knockdown of AT2R prevented leptin-induced cardiomyocyte hypertrophy in vitro. Collectively, our results suggest that AT2R is involved in obesity-induced cardiac hypertrophy.
    Keywords angiotensin II ; animal disease models ; body weight changes ; cardiomyocytes ; diet ; glucose ; hypercholesterolemia ; hypertrophy ; males ; mice ; obesity ; risk factors
    Language English
    Dates of publication 2019-0909
    Publishing place Elsevier B.V.
    Document type Article
    Note Pre-press version
    ZDB-ID 187438-x
    ISSN 1872-8057 ; 0303-7207
    ISSN (online) 1872-8057
    ISSN 0303-7207
    DOI 10.1016/j.mce.2019.110576
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Age-related changes in vascular responses to angiotensin-(1-7) in female mice.

    Costa-Fraga, Fabiana P / Goncalves, Gleisy K / Souza-Neto, Fernando P / Reis, Adelina M / Capettini, Luciano As / Santos, Robson As / Fraga-Silva, Rodrigo A / Stergiopulos, Nikolaos / da Silva, Rafaela F

    Journal of the renin-angiotensin-aldosterone system : JRAAS

    2018  Volume 19, Issue 3, Page(s) 1470320318789332

    Abstract: The vasodilatory effect of angiotensin-(1-7) seems to vary between sexes, and estradiol (E2) can modulate the magnitude of the Ang-(1-7) vasodilatory response in female rats. However, there are few studies addressing the influence of sex on the age- ... ...

    Abstract The vasodilatory effect of angiotensin-(1-7) seems to vary between sexes, and estradiol (E2) can modulate the magnitude of the Ang-(1-7) vasodilatory response in female rats. However, there are few studies addressing the influence of sex on the age-related vasodilatory effect of Ang-(1-7). Here, we evaluated the vasodilatory response to Ang-(1-7) on vascular ageing. Ang-(1-7) dose-response curves were determined in mice aortic rings from males (old and young) and females (E2 treated/non-treated old and young) mounted in an isolated organ chamber. Abdominal aortic rings were used for protein expression analysis and determination of reactive oxygen species (ROS) and nitric oxide (NO) production. Our results showed that the Ang-(1-7) vasodilatory effect was absent in aorta from old females, contrasting with a full response in vessels from young females. The Ang-(1-7) vasodilatory effect was restored by E2 replacement in old females. A robust increase in Mas receptor, SOD2, NRF-2 and NOX2 expression was observed in aorta from old females, which was normalized by E2. This effect of E2 was also associated with lower production of ROS and normal levels of NO. In conclusion, our data demonstrated that pathways involved in the Ang-(1-7) vasodilatory response in female mice is affected by hormonal changes in ageing and rescued by E2.
    MeSH term(s) Aging/metabolism ; Angiotensin I/pharmacology ; Animals ; Aorta/metabolism ; Blood Vessels/metabolism ; Blood Vessels/pathology ; Estradiol/pharmacology ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Models, Biological ; Nitric Oxide/metabolism ; Oxidative Stress/drug effects ; Peptide Fragments/pharmacology ; Superoxides/metabolism ; Vasodilation/drug effects
    Chemical Substances Peptide Fragments ; Superoxides (11062-77-4) ; Nitric Oxide (31C4KY9ESH) ; Estradiol (4TI98Z838E) ; Angiotensin I (9041-90-1) ; angiotensin I (1-7) (IJ3FUK8MOF)
    Language English
    Publishing date 2018-07-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 2086948-4
    ISSN 1752-8976 ; 1470-3203
    ISSN (online) 1752-8976
    ISSN 1470-3203
    DOI 10.1177/1470320318789332
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Are Agonistic Autoantibodies against G-Protein Coupled Receptors Involved in the Development of Long-Term Side Effects of Tumor Chemotherapy?

    Haberland, Annekathrin / Santos, Robson A.S. / Schimke, Ingolf / Wallukat, Gerd

    Case Reports in Oncology

    2013  Volume 6, Issue 1, Page(s) 104–108

    Abstract: Metabolic syndrome and cardiomyopathies are long-term consequences of chemo- and radiotherapy and develop long after completing the initial tumor treatment. The slow progression of such late effects might be an indication of the involvement of autoimmune ...

    Institution Charité - Universitätsmedizin Berlin, and Max-Delbrück-Center for Molecular Medicine, Berlin, Germany National Institute of Science and Technology in Nanobiopharmaceuticals and Federal University of Minas Gerais, Belo Horizonte, Brazil
    Abstract Metabolic syndrome and cardiomyopathies are long-term consequences of chemo- and radiotherapy and develop long after completing the initial tumor treatment. The slow progression of such late effects might be an indication of the involvement of autoimmune processes in the development of such follow-up consequences. Functionally active autoantibodies, which permanently stimulate relevant cell receptors, might be a crucial component. Here, we report the detection of functionally active agonistic autoantibodies such as the autoantibody against the adrenergic alpha1-receptor, the muscarinic M2-receptor, and the newly discovered autoantibody against the Mas-receptor in the plasma of a cancer survivor following chemotherapy treatment.
    Keywords Agonistic autoantibodies ; G-protein coupled receptor autoantibodies ; Chemotherapy ; Tumor therapy ; Cardiomyopathy ; Metabolic syndrome ; Long-term disturbances
    Language English
    Publishing date 2013-02-21
    Publisher S. Karger AG
    Publishing place Basel, Switzerland
    Document type Article
    ZDB-ID 2458961-5
    ISSN 1662-6575 ; 1662-6575
    ISSN (online) 1662-6575
    ISSN 1662-6575
    DOI 10.1159/000348425
    Database Karger publisher's database

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  8. Article: Mas receptors in modulating relaxation induced by perivascular adipose tissue

    Lee, Robert M.K.W / Bader, Michael / Alenina, Natalia / Santos, Robson A.S / Gao, Yu-Jing / Lu, Chao

    Life sciences. 2011 Sept. 26, v. 89, no. 13-14

    2011  

    Abstract: AIMS: Perivascular adipose tissue (PVAT) is known to secrete vascular relaxation factors, and angiotensin 1–7 [Ang-(1–7)] acting on the endothelium is one of the endothelium-dependent relaxation factors. Mas protein is the receptor for Ang-(1–7). Using ... ...

    Abstract AIMS: Perivascular adipose tissue (PVAT) is known to secrete vascular relaxation factors, and angiotensin 1–7 [Ang-(1–7)] acting on the endothelium is one of the endothelium-dependent relaxation factors. Mas protein is the receptor for Ang-(1–7). Using aorta from Mas-knockout (K/O) and wild type (FVB) mice, we wished to establish the essential role of Mas receptors in mediating the endothelium-dependent relaxation response induced by relaxation factors from PVAT. MAIN METHODS: Thoracic aortic rings from K/O and FVB mice were prepared with or without PVAT (PVAT+ and PVAT−) and/or intact endothelium (E+) or with the endothelium removed (E−) for functional studies. The contraction and relaxation responses of these vessels to agonist in the presence of different receptor antagonists were studied. KEY FINDINGS: PVAT attenuated the contraction induced by phenylephrine (PHE) in the presence of endothelium only in vessels from FVB mice. Mas receptor antagonists D-Ala-Ang-(1–7) (A779) or D-Pro⁷-Ang-(1–7) enhanced the contraction induced by PHE only in vessels from FVB mice. Ang-(1–7) caused a relaxation response only in E+vessels from FVB mice. Transfer of donor solution from PVAT+ vessels to PVAT− recipient vessels caused a relaxation response among FVB vessels and not among vessels from K/O mice. SIGNIFICANCE: Mas receptors are essential in mediating the endothelium-dependent relaxation response induced by PVAT, therefore highlighting the important role of Ang-(1–7) in the control of vascular functions through PVAT.
    Keywords adipose tissue ; agonists ; antagonists ; aorta ; endothelium ; mice ; phenylephrine ; receptors
    Language English
    Dates of publication 2011-0926
    Size p. 467-472.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 3378-9
    ISSN 1879-0631 ; 0024-3205
    ISSN (online) 1879-0631
    ISSN 0024-3205
    DOI 10.1016/j.lfs.2011.07.016
    Database NAL-Catalogue (AGRICOLA)

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  9. Article: Supramolecular interactions between losartan and hydroxypropyl-β-CD: ESI mass-spectrometry, NMR techniques, phase solubility, isothermal titration calorimetry and anti-hypertensive studies

    de Paula, Washington X / Denadai, Ângelo M.L / Santoro, Marcelo M / Braga, Aline N.G / Santos, Robson A.S / Sinisterra, Rubén D

    International journal of pharmaceutics. 2011 Feb. 14, v. 404, no. 1-2

    2011  

    Abstract: In this work, low soluble supramolecular complex between the losartan potassium (Los) and hydroxypropil-β-cyclodextrin (HPβCD) were characterized throughout phase-solubility, NMR techniques (¹H and 2D-ROESY) and isothermal titration calorimetry (ITC) in ... ...

    Abstract In this work, low soluble supramolecular complex between the losartan potassium (Los) and hydroxypropil-β-cyclodextrin (HPβCD) were characterized throughout phase-solubility, NMR techniques (¹H and 2D-ROESY) and isothermal titration calorimetry (ITC) in order to attain physical–chemical knowledge of the system. In addition, the hypertensive effect of composition Los/HPβCD was evaluated aiming to obtain a more efficient oral pharmaceutical composition. ESI mass spectrometry and ITC blank experiment demonstrate the presence of Los clusters at 30mM pure solution. Phase-solubility experiments showed a “Bs” type system, due to the formation of a less soluble complex than pure Los. NMR demonstrated the short distance interactions between the Los and the cyclodextrin, where several possibilities of interactions were observed. ITC data suggest an average 1:1 stoichiometry of Los and the cyclodextrin. The complex demonstrated efficiency in hypertension control, presenting antagonist action on the pressure effect of angiotensin II within 30h, as compared to Los alone, 6h, indicating that inclusion of Los in HPβCD enhanced the extent and duration of its antagonistic action. In this work, a model of interaction between Los and HPβCD was proposed based on dissociation of self-assembled Los followed by complexation with HPβCD.
    Keywords angiotensin II ; antagonists ; calorimetry ; dissociation ; hypertension ; mass spectrometry ; models ; nuclear magnetic resonance spectroscopy ; potassium ; solubility ; stoichiometry ; titration
    Language English
    Dates of publication 2011-0214
    Size p. 116-123.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 428962-6
    ISSN 1873-3476 ; 0378-5173
    ISSN (online) 1873-3476
    ISSN 0378-5173
    DOI 10.1016/j.ijpharm.2010.11.008
    Database NAL-Catalogue (AGRICOLA)

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  10. Article: Angiotensin-(1–7) Induces Peripheral Antinociception through Mas Receptor Activation in an Opioid-Independent Pathway

    Costa, Aline C.O. / Becker, Lenice K. / Moraes, Éder R. / Romero, Thiago R.L. / Guzzo, Luciana / Santos, Robson A.S. / Duarte, Igor D.G.

    Pharmacology

    2012  Volume 89, Issue 3-4, Page(s) 137–144

    Abstract: The G protein-coupled receptor Mas was recently described as an angiotensin-(1–7) [Ang-(1–7)] receptor. In the present study, we demonstrate an antinociceptive effect of Ang-(1–7) for the first time. Additionally, we evaluated the anatomical localization ...

    Institution Departments of Pharmacology and Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
    Abstract The G protein-coupled receptor Mas was recently described as an angiotensin-(1–7) [Ang-(1–7)] receptor. In the present study, we demonstrate an antinociceptive effect of Ang-(1–7) for the first time. Additionally, we evaluated the anatomical localization of Mas in the dorsal root ganglia using immunofluorescence. This is the first evidence indicating that this receptor is present in sensitive neurons. The antinociceptive effect was demonstrated using the rat paw pressure test. For this test, sensitivity is increased by intraplantar injection of prostaglandin E2. Ang-(1–7) administered locally into the right hind paw elicited a dose-dependent antinociceptive effect. Because the higher dose of Ang-(1–7) did not produce an effect when injected into the contralateral paw, this effect was considered local. The specific antagonist for the Mas receptor, A-779, inhibited the peripheral antinociception induced by exposure to 4 µg/paw Ang-(1–7) in a dose-dependent manner. The highest dose completely reversed the antinociceptive effect induced by Ang-(1–7), suggesting that the Mas receptor is an obligatory component in this process and that other angiotensin receptors may not be involved. When injected alone, the antagonist was unable to induce hyperalgesia or antinociception. Alternatively, naloxone was unable to inhibit the antinociceptive effect induced by Ang-(1–7), suggesting that endogenous opioid peptides may not be involved in this response. These data provide the first anatomical basis for the physiological role of Ang-(1–7) in the modulation of pain perception via Mas receptor activation in an opioid-independent pathway. Taken together, these results provide new perspectives for the development of a new class of analgesic drugs.
    Keywords Angiotensin ; Mas receptor ; A-779 ; Peripheral antinociception ; Prostaglandin ; Immunofluorescence
    Language English
    Publishing date 2012-03-12
    Publisher S. Karger AG
    Publishing place Basel, Switzerland
    Document type Article
    Note Original Paper
    ZDB-ID 206671-3
    ISSN 1423-0313 ; 0031-7012
    ISSN (online) 1423-0313
    ISSN 0031-7012
    DOI 10.1159/000336340
    Database Karger publisher's database

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