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Mehdi Nematbakhsh, Azam Mansouri
Recently a cross talk between angiotensin 1-7 (Ang1-7) receptor (MasR) and angiotensin II receptors types 1 and 2 (AT1R and AT2R) has been highlighted. The effects of MasR antagonist (A779) compared to the vehicle on the renal blood flow (RBF) and renal vascular resistance (RVR) responses to Ang1-7 (300 ng/kg/min) infusion in the absence of Ang II receptors in male and female rats were determined at controlled renal perfusion pressure. Ang1-7 infusion did not alter mean arterial pressure in male and female rats...
April 2018: Research in Pharmaceutical Sciences
Mostafa A Rabie, Mai A Abd El Fattah, Noha N Nassar, Hanan S El-Abhar, Dalaal M Abdallah
MAS receptor (MASR), expressed in several brain areas, conferred neuroprotection against neurodegenerative disorders when activated by angiotensin (Ang) 1-7; however, its role in Parkinson's disease (PD) remains elusive. Intra-striatal post-administration of Ang1-7, using a 6-hydroxydopamine (OHDA) PD model, improved motor performance and muscle coordination. On the molecular level, Ang1-7 upregulated the striatal expression of MASR and caused upsurge in its downstream targets (p-PI3K/p-Akt/p-CREB/BDNF) to phosphorylate TrKB, which in a positive feedback upregulates MASR...
May 2018: Biochemical Pharmacology
Marta Kuczeriszka, Elzbieta Kompanowska-Jezierska, Janusz Sadowski, Minolfa C Prieto, L Gabriel Navar
BACKGROUND: Indirect evidence suggests that angiotensin 1-7 (Ang1-7) may counterbalance prohypertensive actions of angiotensin II (AngII), via activation of vascular and/or renal tubular receptors to cause vasodilation and natriuresis/diuresis. We examined if Ang1-7 would attenuate the development of hypertension, renal vasoconstriction, and decreased natriuresis in AngII-infused rats and evaluated the mechanisms involved. METHODS: AngII, alone or with Ang1-7, was infused to conscious Sprague-Dawley rats for 13 days and systolic blood pressure (SBP) and renal excretion were repeatedly determined...
March 10, 2018: American Journal of Hypertension
Rachel Hamias, Assaf Rudich, George Greenberg, Gabriel Szendro, Talya Wolak
OBJECTIVE AND DESIGN: Evaluating the pro-/anti-inflammatory activity of the C-terminal cleavage product of osteopontin in comparison to angiotensin 1-7. MATERIAL AND SUBJECTS: Human coronary endothelial cells (hcEC) treated with conditioned media from human U937 macrophages. TREATMENT: Macrophages were (pre)treated with C-terminal, full-length or N-terminal osteopontin (OPN-C, OPN-FL, OPN-N, respectively), angiotensin II, angiotensin 1-7 or TNF-α...
March 2018: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Bogusz Trojanowicz, Christof Ulrich, Roman Fiedler, Peter Martus, Markus Storr, Torsten Boehler, Kristin Werner, Michael Hulko, Daniel Zickler, Kevin Willy, Ralf Schindler, Matthias Girndt
Background: High mortality of haemodialysis patients is associated with systemic chronic inflammation and overactivation of the renin-angiotensin system (RAS). Insufficient elimination of pro-inflammatory immune mediators, especially in the molecular weight range of 15-45 kDa, may be one of the reasons for this. Employment of haemodialysis membranes with increased permeability was shown to ameliorate the inflammatory response and might modulate the effects of local RAS. In this study, we tested the impact of high cut-off (HCO), medium cut-off (MCO) and high-flux (HF) dialysis on leucocytic transcripts of angiotensin-converting enzymes (ACE and ACE2)...
July 19, 2017: Nephrology, Dialysis, Transplantation
Kamila Domińska, Antoni Kowalski, Tomasz Ochędalski, Elżbieta Rębas
Angiotensin II (AngII), the main peptide of the renin‑angiotensin system (RAS), is involved in the proliferation of different types of cells, normal and pathological as well. The protein tyrosine kinases (PTKs) play an important role in the growth, differentiation and apoptosis of cells. AngII action depends on the hormonal milieu of the cell, and on sex steroid influence. Angiotensin 1‑7 (Ang1‑7), metabolite of AngII, shows opposite action to AngII in cells. The present study aimed to examine the influence of 17β‑estradiol and testosterone on AngII and Ang1‑7 action on PTK activity in androgen‑independent humane prostate cancer cell line DU145...
September 25, 2017: International Journal of Molecular Medicine
Larissa B Teixeira, Lucas T Parreiras-E-Silva, Thiago Bruder-Nascimento, Diego A Duarte, Sarah C Simões, Rafael M Costa, Deisy Y Rodríguez, Pedro A B Ferreira, Carlos A A Silva, Emiliana P Abrao, Eduardo B Oliveira, Michel Bouvier, Rita C Tostes, Claudio M Costa-Neto
The renin-angiotensin system (RAS) plays a key role in the control of vasoconstriction as well as sodium and fluid retention mediated mainly by angiotensin (Ang) II acting at the AT1 receptor (AT1R). Ang-(1-7) is another RAS peptide, identified as the endogenous ligand of the Mas receptor and known to counterbalance many of the deleterious effects of AngII. AT1R signaling triggered by β-arrestin-biased agonists has been associated to cardioprotection. Because position 8 in AngII is important for G protein activation, we hypothesized that Ang-(1-7) could be an endogenous β-arrestin-biased agonist of the AT1R...
September 19, 2017: Scientific Reports
Hatem M Abuohashish, Mohammed M Ahmed, Dina Sabry, Mahmoud M Khattab, Salim S Al-Rejaie
The local role of the renin angiotensin system (RAS) was documented recently beside its conventional systemic functions. Studies showed that the effector angiotensin II (AngII) alters bone health, while inhibition of the angiotensin converting enzyme (ACE-1) preserved these effects. The newly identified Ang1-7 exerts numerous beneficial effects opposing the AngII. Thus, the current study examines the role of Ang1-7 in mediating the osteo-preservative effects of ACEI (captopril) through the G-protein coupled Mas receptor using an ovariectomized (OVX) rat model of osteoporosis...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Roberto Schreiber, Layde R Paim, Guilherme de Rossi, José R Matos-Souza, Anselmo de A Costa E Silva, Cláudio D Nogueira, Eliza R Azevedo, Karina C Alonso, Zaira Palomino, Andrei C Sposito, Dulce E Casarini, José I Gorla, Alberto Cliquet, Wilson Nadruz
Chronic spinal cord injury (SCI) is often associated with reductions in left ventricular (LV) diastolic function. Impairments in sympathetic activity and activation of the renin-angiotensin system are reported in SCI individuals and may hypothetically be implicated in this association. Hence, the present study verified the relationship between these two neuro-hormonal and cardiac functional and structural characteristics in SCI individuals. Twenty-two men with SCI (injury level above T6 and no voluntary motion below the injury) and 11 able-bodied men were evaluated by clinical, hemodynamic, laboratory, and echocardiographic analysis and had plasmatic renin, angiotensin I (ANGI), angiotensin II (ANGII), angiotensin 1-7 (ANG1-7), and noradrenaline levels measured...
August 1, 2017: Journal of Neurotrauma
Hatem M Abuohashish, Mohammed M Ahmed, Dina Sabry, Mahmoud M Khattab, Salim S Al-Rejaie
The renin angiotensin system (RAS) regulates numerous systemic functions and is expressed locally in skeletal tissues. Angiotensin1-7 (Ang1-7) is a beneficial member of the RAS, and the therapeutic effects of a large number of angiotensin receptors blockers (ARBs) are mediated by an Ang1-7-dependent cascade. This study examines whether the reported osteo-preservative effects of losartan are mediated through the angiotensin converting enzyme2 (ACE-2)/Ang1-7/Mas pathway in ovariectomized (OVX) rats. Sham and OVX animals received losartan (10mg/kg/d p...
July 15, 2017: European Journal of Pharmacology
L Anguiano, M Riera, J Pascual, M J Soler
Angiotensin converting enzyme (ACE) 2 is a homologue of ACE that catalyzes the conversion of Angiotensin (Ang) II into Ang1-7, which induces vasodilation, anti-fibrotic, anti-proliferative and anti-inflammatory effects. Given that ACE2 counterbalances the effects of Ang II, it has been proposed as a biomarker in kidney disease patients. Circulating ACE2 has been studied in human and experimental studies under physiological and pathological conditions and different techniques have been assessed to determine its enzymatic activity...
2017: Current Medicinal Chemistry
Waheed Asghar, Ali Aghazadeh-Habashi, Fakhreddin Jamali
A co-morbidity of inflammatory conditions is increased cardio-renal risks. Additionally, nonsteroidal anti-inflammatory drugs (NSAIDs) which are used to treat pain and inflammation are also associated with increase in such risks. We hypothesized that inflammation and NSAIDs impose the cardio-renal risk through the activation of the renin-angiotensin-system (RAS), a regulating pathway of the renal and cardiovascular homeostasis. We investigated the effect of adjuvant arthritis and NSAIDs on the RAS. Western blotting and ELISA were used to measure the RAS components...
April 7, 2017: Inflammopharmacology
Kun Wang, Xiaoqian Liu, Hang Xiao, Huanhuan Wang, Yuanshu Zhang
Renin-angiotensin system (RAS) plays an important role of regulating inflammatory injury. However, it is not clear about the correlation between renin-angiotensin system (RAS) and inflammation induced by LPS in mammary gland cells. So immunofluorescence was performed to verify the ACE2 expression in mammary gland cells. MTT assay was performed to detect cell viability. ELISA was performed to detect cytokines in cell supernatant. Western Blot was performed to analyze RAS levels and ACE2 level change was observed by immunofluorescence...
May 2017: International Immunopharmacology
Hang Nguyen, Bruce D Uhal
Recent work from this laboratory showed that endoplasmic reticulum (ER) stress-induced apoptosis of alveolar epithelial cells (AECs) is regulated by the autocrine angiotensin (ANG)II/ANG1-7 system. The proteasome inhibitor MG132 or surfactant protein C (SP-C) BRICHOS domain mutation G100S induced apoptosis in human AECs by activating the proapoptotic cathepsin D and reducing antiapoptotic angiotensin converting enzyme-2 (ACE-2). This study tested the hypothesis that ER stress-induced apoptosis of human AECs might be mediated by influence of the unfolded protein response (UPR) on the autocrine ANGII/ANG1-7 system...
November 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
R Hmazzou, A Flahault, Y Marc, C Llorens-Cortes
OBJECTIVE: In the brain, angiotensin III (AngIII) generated from angiotensin II (AngII) by aminopeptidase A (APA) exerts a tonic stimulatory action on the control of blood pressure (BP) in hypertensive rats. Inhibition of brain APA by RB150 (also known as QGC001), an orally active prodrug of the specific and selective APA inhibitor EC33, blocks brain AngIII formation and normalizes BP in hypertensive rats. Thus, RB150 has emerged as the prototype of a new class of centrally-acting antihypertensive agents and is currently evaluated in a phase II clinical trial in hypertensive patients...
September 2016: Journal of Hypertension
Maryam Maleki, Mehdi Nematbakhsh
Background. Angiotensin 1-7 (Ang1-7) plays an important role in renal circulation. Hemorrhagic shock (HS) may cause kidney circulation disturbance, and this study was designed to investigate the renal blood flow (RBF) response to Ang1-7 after HS. Methods. 27 male Wistar rats were subjected to blood withdrawal to reduce mean arterial pressure (MAP) to 45 mmHg for 45 min. The animals were treated with saline (group 1), Ang1-7 (300 ng·kg(-1) min(-1)), Ang1-7 in hypertonic sodium chloride 7.5% (group 3), and hypertonic solution alone (group 4)...
2016: International Journal of Vascular Medicine
Maitham A Khajah, Maryam M Fateel, Kethireddy V Ananthalakshmi, Yunus A Luqmani
BACKGROUND: There is evidence to support a role for angiotensin (Ang) 1-7 in reducing the activity of inflammatory signaling molecules such as MAPK, PKC and SRC. Enhanced angiotensin converting enzyme 2 (ACE2) expression has been observed in patients with inflammatory bowel disease (IBD) suggesting a role in its pathogenesis, prompting this study. METHODS: The colonic expression/activity profile of ACE2, Ang 1-7, MAS1-receptor (MAS1-R), MAPK family and Akt were determined by western blot and immunofluorescence...
2016: PloS One
Indiwari Gopallawa, Bruce D Uhal
Earlier work from this laboratory showed that autocrine generation of angiotensin II and c-Jun-NH2-terminal kinase phosphorylation (p-JNK) are both required events in alveolar epithelial cell (AEC) apoptosis. Although earlier data showed that angiotensin-(1-7) [ANG-(1-7)] protects against AEC apoptosis, the pathways by which ANG-(1-7)/mas activation prevent JNK phosphorylation and apoptosis are poorly understood. Therefore, in the current study, it was theorized that ANG-(1-7) activates a mitogen-activated protein kinase phosphatase (MKP) and thereby reduces JNK phosphorylation to inhibit apoptosis and promote cell survival...
February 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Fleur Bossi, Stella Bernardi, Daniele De Nardo, Alessandra Bramante, Riccardo Candido, Renzo Carretta, Fabio Fischetti, Bruno Fabris
OBJECTIVE: Recent studies have demonstrated that Ang1-7 has anti-inflammatory effects. Since the formation of Ang1-7 is significantly altered in the setting of diabetes, here we aimed to evaluate whether Ang1-7 infusion could ameliorate diabetes-induced leukocyte recruitment. METHODS: Wild-type male Wistar rats were randomly allocated to the following groups: control + saline, control + Ang1-7, diabetes + saline, diabetes + Ang1-7. Diabetes was induced by streptozotocin...
January 2016: Atherosclerosis
Aghdas Dehghani, Shadan Saberi, Mehdi Nematbakhsh
Background. The accompanied role of Mas receptor (MasR), bradykinin (BK), and female sex hormone on renal blood flow (RBF) response to angiotensin 1-7 is not well defined. We investigated the role of MasR antagonist (A779) and BK on RBF response to Ang 1-7 infusion in ovariectomized estradiol-treated rats. Methods. Ovariectomized Wistar rats received estradiol (OVE) or vehicle (OV) for two weeks. Catheterized animals were subjected to BK and A799 infusion and mean arterial pressure (MAP), RBF, and renal vascular resistance (RVR) responses to Ang 1-7 (0, 100, and 300 ng kg(-1) min(-1)) were determined...
2015: Advances in Pharmacological Sciences
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