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Ang 2 AND nitric oxide

Andrea L Conroy, Michael Hawkes, Chloe R McDonald, Hani Kim, Sarah J Higgins, Kevin R Barker, Sophie Namasopo, Robert O Opoka, Chandy C John, W Conrad Liles, Kevin C Kain
Background.  Host responses to infection are critical determinants of disease severity and clinical outcome. The development of tools to risk stratify children with malaria is needed to identify children most likely to benefit from targeted interventions. Methods.  This study investigated the kinetics of candidate biomarkers of mortality associated with endothelial activation and dysfunction (angiopoietin-2 [Ang-2], soluble FMS-like tyrosine kinase-1 [sFlt-1], and soluble intercellular adhesion molecule-1 [sICAM-1]) and inflammation (10 kDa interferon γ-induced protein [CXCL10/IP-10] and soluble triggering receptor expressed on myeloid cells-1 [sTREM-1]) in the context of a randomized, double-blind, placebo-controlled, parallel-arm trial evaluating inhaled nitric oxide versus placebo as adjunctive therapy to parenteral artesunate for severe malaria...
September 2016: Open Forum Infectious Diseases
Ming Li, Thor Tejada, Jonathan P Lambert, Chad K Nicholson, Eiji Yahiro, Vats T Ambai, Syeda F Ali, Eddie W Bradley, Robert M Graham, Louis J Dell'Italia, John W Calvert, Nawazish Naqvi
Angiotensin II (Ang II) modulates blood pressure and atherosclerosis development through its vascular type-1 (AT1R) and type-2 (AT2R) receptors, which have opposing effects. AT2R activation produces hypotension, and is anti-atherogenic. Targeted overexpression of AT2Rs in vascular smooth muscle cells (VSMCs) indicates that these effects are due to increased nitric oxide (NO) generation. However, the role of endogenous VSMC AT2Rs in these events is unknown. Effect of 7-day low-dose Ang II-infusion (12 µg/kg/hr) on blood pressure was tested in 9-week-old apoE((-/-)) mice fed a low or high cholesterol diet (LCD or HCD, respectively)...
2016: American Journal of Cardiovascular Disease
Šárka Doleželová, Šárka Jíchová, Zuzana Husková, Alžběta Vojtíšková, Petr Kujal, Lenka Hošková, Josef Kautzner, Janusz Sadowski, Luděk Červenka, Libor Kopkan
The fawn-hooded hypertensive (FHH) rat serves as a genetic model of spontaneous hypertension associated with glomerular hyperfiltration and proteinuria. However, the knowledge of the natural course of hypertension and kidney disease in FHH rats remains fragmentary and the underlying pathophysiological mechanisms are unclear. In this study, over the animals' lifetime, we followed the survival rate, blood pressure (telemetry), indices of kidney damage, the activity of renin-angiotensin (RAS) and nitric oxide (NO) systems, and CYP450-epoxygenase products (EETs)...
2016: Clinical and Experimental Hypertension: CHE
Robert M Carey
The renin-angiotensin system (RAS) is arguably the most important and best studied hormonal system in the control of blood pressure (BP) and the pathogenesis of hypertension. The RAS features its main effector angiotensin II (Ang II) acting via its 2 major receptors, angiotensin type-1(AT1R) and type-2 (AT2R). In general, AT2Rs oppose the detrimental actions of Ang II via AT1Rs. AT2R activation induces vasodilation and natriuresis, but its effects to lower BP in hypertension have not been as clear as anticipated...
September 24, 2016: American Journal of Hypertension
Lamei Yu, Kuichang Yuan, Hoang Thi Ai Phuong, Byung Mun Park, Suhn Hee Kim
Angiotensin-(1-5) [Ang-(1-5)], which is a metabolite of Angiotensin-(1-7) [Ang-(1-7)] catalyzed by angiotensin-converting enzyme (ACE), is a pentapeptide of the renin-angiotensin system (RAS). It has been reported that Ang-(1-7) and Ang-(1-9) stimulate the secretion of atrial natriuretic peptide (ANP) via Mas receptor (Mas R) and Ang II type 2 receptor (AT2R), respectively. However, it still remains unknown whether Ang-(1-5) has a similar function to Ang-(1-7). We investigated the effect of Ang-(1-5) on ANP secretion and to define its signaling pathway using isolated perfused beating rat atria...
September 20, 2016: Peptides
Jonathan Adam, Stefan Brandmaier, Jörn Leonhardt, Markus F Scheerer, Robert P Mohney, Tao Xu, Jie Bi, Markus Rotter, Martina Troll, Shen Chi, Margit Heier, Christian Herder, Wolfgang Rathmann, Guido Giani, Jerzy Adamski, Thomas Illig, Konstantin Strauch, Yixue Li, Christian Gieger, Annette Peters, Karsten Suhre, Donna Ankerst, Thomas Meitinger, Martin Hrabe de Angelis, Michael Roden, Susanne Neschen, Gabi Kastenmüller, Rui Wang-Sattler
Metformin is the first-line oral medication to increase insulin sensitivity in patients with type 2 diabetes (T2D). Our aim is to investigate metformin's pleiotropic effect using a non-targeted metabolomics approach. We analyzed 353 metabolites in fasting serum samples of the population-based human KORA F4 cohort. To compare T2D patients treated with metformin (mt-T2D, n=74) and those without antidiabetic medication (ndt-T2D, n=115), we used multivariable linear regression models in a cross-sectional study...
September 12, 2016: Diabetes
Yusof Kamisah, Shu-Min Ang, Faizah Othman, Badlishah Sham Nurul-Iman, Hj Mohd Saad Qodriyah
Virgin coconut oil, rich in antioxidants, was shown to attenuate hypertension. This study aimed to investigate the effects of virgin coconut oil on blood pressure and related parameters in kidneys in rats fed with 5-times-heated palm oil (5HPO). Thirty-two male Sprague-Dawley rats were divided into 4 groups. Two groups were fed 5HPO (15%) diet and the second group was also given virgin coconut oil (1.42 mL/kg, oral) daily for 16 weeks. The other 2 groups were given basal diet without (control) and with virgin coconut oil...
October 2016: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
Ji Young Lee, Helena M Linge, Kanta Ochani, Ke Lin, Edmund J Miller
INTRODUCTION: Sepsis is characterized by dysregulated systemic inflammation and cytokine storm. Angiopoietin-2 (Ang-2) is known to closely correlate with severity of sepsis-related acute lung injury and mortality. The aim of this study was to clarify the mechanisms involved in Ang-2 secretion to better understand the pathophysiology of sepsis. MATERIALS AND METHODS: The concentration of Ang-2 was assessed in culture medium of pulmonary microvascular endothelial cells in the presence or absence of Gram-positive bacteria cell wall components [lipoteichoic acid (LTA) and peptidoglycan (PGN)] stimulation at different time points ranging from 15 minutes to 24 hours...
September 1, 2016: Experimental Lung Research
Zoran Miloradović, Milan Ivanov, Đurđica Jovović, Danijela Karanović, Una Jovana Vajić, Jasmina Marković-Lipkovski, Nevena Mihailović-Stanojević, Jelica Grujić Milanović
Many studies demonstrated that angiotensin 2 type 1 receptor (AT1R) blockade accelerates renal recovery in post-ischaemic kidney but there are many controversies related to its net effect on kidney structure and function. During the past years, our research group was trying to define the pathophysiological significance of the renin-angiotensin system on post-ischemic acute renal failure (ARF) development in normotensive Wistar as well as hypertensive rats (SHR). This review mostly summarizes our experience in that field...
August 18, 2016: Journal of Physiology and Biochemistry
C F Sun, S G Wang, Y G Peng, Y Shi, Y P Du, G X Shi, T Wen, Y K Wang, H Su
OBJECTIVE: To investigate the effects of different drugs on systolic blood pressure (SBP) and left ventricular hypertrophy (LVH) in spontaneously hypertensive rats under cold stress. METHODS: A total of 40 male spontaneously hypertensive rats aged 10 weeks (160~200 g) were given adaptive feeding for 7 days at a temperature of 20±1°C and then randomly divided into control group, cold stress group, metoprolol group, amlodipine group, and benazepril group, with 8 rats in each group...
June 20, 2016: Chinese Journal of Industrial Hygiene and Occupational Diseases
Yebo Zhou, Zhiyuan Wu, Xu Cao, Lei Ding, ZhengShun Wen, Jin-Song Bian
Both hydrogen sulfide (H2S) and nitric oxide (NO) are important gaseous mediators. We and others previously reported that these two gases react with each other to generate a new mediator, nitroxyl (HNO), and regulate cardiovascular functions. In this study, we demonstrated for the first time that the interaction between the two gases also existed in microglia. The biological functions of HNO in microglial cells were further studied with Angeli's salt (AS), an HNO donor. We found that AS attenuated lipopolysaccharide (LPS)-evoked production of reactive oxygen species (ROS) and pro-inflammatory cytokines (e...
September 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Eliza Julia Pedraza-Brindis, Karina Sánchez-Reyes, Georgina Hernández-Flores, Alejandro Bravo-Cuellar, Luis Felipe Jave-Suárez, Adriana Aguilar-Lemarroy, Paulina Gómez-Lomelí, Brenda Anahí López-López, Pablo Cesar Ortiz-Lazareno
Patients with cervical cancer (CxCa) typically present an infiltrate of tumor-associated macrophages, which is associated with a poor prognosis. We found that CxCa cell lines (HeLa, SiHa, and C-33A) secreted factors involved in regulating tumor growth including IL-6, IL-4, PDGFAA, HGF, VEGF, ANG-2, and TGF-β3. We assessed the effects of culture supernatants from these cell lines on macrophages derived from the THP-1 cell line. Macrophages treated with culture supernatants from CxCa cells developed an M2-like phenotype with expression of CD163, low nitric oxide release, and high secretion of IL-6, PDGFAA, HGF, ANG-2, and VEGF...
July 16, 2016: Cellular Immunology
Michael Hezel, Maria Peleli, Ming Liu, Christa Zollbrecht, Boye L Jensen, Antonio Checa, Alessia Giulietti, Craig E Wheelock, Jon O Lundberg, Eddie Weitzberg, Mattias Carlström
Advanced age is associated with increased risk for cardiovascular disease and type 2 diabetes. A proposed central event is diminished amounts of nitric oxide (NO) due to reduced generation by endothelial NO synthase (eNOS) and increased oxidative stress. In addition, it is widely accepted that increased angiotensin II (ANG II) signaling is also implicated in the pathogenesis of endothelial dysfunction and hypertension by accelerating formation of reactive oxygen species. This study was designed to test the hypothesis that dietary nitrate supplementation could reduce blood pressure and improve glucose tolerance in aged rats, via attenuation of NADPH oxidase activity and ANG II receptor signaling...
July 26, 2016: Free Radical Biology & Medicine
T Michael De Silva, Dale A Kinzenbaw, Mary L Modrick, Lindsey D Reinhardt, Frank M Faraci
Rho kinase (ROCK) has been implicated in physiological and pathophysiological processes, including regulation of vascular function. ROCK signaling is thought to be a critical contributor to cardiovascular disease, including hypertension and effects of angiotensin II (Ang II). Two isoforms of ROCK (1 and 2) have been identified and are expressed in vascular cells. In this study, we examined the importance of ROCK2 in relation to vessel function using several models and a novel inhibitor of ROCK2. First, incubation of carotid arteries with the direct RhoA activator CN-03 or Ang II impaired endothelium-dependent relaxation by ≈40% to 50% (P<0...
September 2016: Hypertension
Sha Sha, Dandan Xu, Yanwei Wang, Weifang Zhao, Xiaoni Li
Fargesin, a bioactive neolignan isolated from magnolia plants, is widely used in the treatment of managing rhinitis, inflammation, histamine, sinusitis, and headache. To provide more biological information about fargesin, we investigated the effects of fargesin on rat aortic rings and 2-kidney, 1-clip (2K1C) hypertensive rats. In vitro, fargesin caused concentration-dependent vasorelaxation in rat isolated aortic rings induced by KCl and norepinephrine. The effect was weakened by endothelium denudation and nitric oxide (NO) synthesis inhibition...
August 2016: Canadian Journal of Physiology and Pharmacology
Hye Eun Yoon, Eun Nim Kim, Min Young Kim, Ji Hee Lim, In-Ae Jang, Tae Hyun Ban, Seok Joon Shin, Cheol Whee Park, Yoon Sik Chang, Bum Soon Choi
Background. This study evaluated whether the change in the renin-angiotensin system (RAS) is associated with arterial aging in mice. Methods. Histologic changes and expressions of transforming growth factor-β (TGF-β), collagen IV, fibronectin, angiotensin II (Ang II), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), prorenin receptor (PRR), Mas receptor (MasR), endothelial nitric oxide synthase (eNOS), NADPH oxidase 2 and oxidase 4 (Nox2 and Nox4), 8-hydroxy-2'-deoxyguanosine (8-OHdG), 3-nitrotyrosine, and superoxide dismutase 1 and dismutase 2 (SOD1 and SOD2) were measured in the thoracic aortas from 2-month-old, 12-month-old, and 24-month-old C57/BL6 mice...
2016: Oxidative Medicine and Cellular Longevity
Lorenzo A Calò, Paul A Davis, Giuseppe Maiolino, Elisa Pagnin, Verdiana Ravarotto, Elena Naso, Gianni Carraro, Agostino Naso
HYPOTHESIS/INTRODUCTION: Angiotensin II (Ang II) has been shown to control erythropoietin (EPO) synthesis as Ang II type 1 receptor (AT1R) blockers block Ang-II-induced EPO oversecretion. To further explore the involvement of AT1R in processes controlling EPO levels, plasma EPO and mononuclear cell NADPH oxidase 4 (NOX4) - a NOX family member involved in oxygen sensing, which is a process central to controlling EPO levels - were assessed in Bartter's/Gitelman's syndrome (BS/GS) patients, a human model of endogenous AT1R antagonism and healthy subjects...
December 2015: Cardiorenal Medicine
Hemant Kumar, Alexander E Ropper, Soo-Hong Lee, Inbo Han
The blood-spinal cord barrier (BSCB) is a specialized protective barrier that regulates the movement of molecules between blood vessels and the spinal cord parenchyma. Analogous to the blood-brain barrier (BBB), the BSCB plays a crucial role in maintaining the homeostasis and internal environmental stability of the central nervous system (CNS). After spinal cord injury (SCI), BSCB disruption leads to inflammatory cell invasion such as neutrophils and macrophages, contributing to permanent neurological disability...
May 18, 2016: Molecular Neurobiology
Matthew J Durand, Natalya S Zinkevich, Michael Riedel, David D Gutterman, Victoria L Nasci, Valerie K Salato, John B Hijjawi, Charles F Reuben, Paula E North, Andreas M Beyer
OBJECTIVE: This study examined vascular actions of angiotensin 1-7 (ANG 1-7) in human atrial and adipose arterioles. APPROACH AND RESULTS: The endothelium-derived hyperpolarizing factor of flow-mediated dilation (FMD) switches from antiproliferative nitric oxide (NO) to proatherosclerotic hydrogen peroxide in arterioles from humans with coronary artery disease (CAD). Given the known vasoprotective properties of ANG 1-7, we tested the hypothesis that overnight ANG 1-7 treatment restores the NO component of FMD in arterioles from patients with CAD...
June 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Chaoming Zhou, Swarna S Ramaswamy, Derrick E Johnson, Dario A Vitturi, Franciso J Schopfer, Bruce A Freeman, Andy Hudmon, Edwin S Levitan
Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) oxidation controls excitability and viability. While hydrogen peroxide (H2O2) affects Ca(2+)-activated CaMKII in vitro, Angiotensin II (Ang II)-induced CaMKIIδ signaling in cardiomyocytes is Ca(2+) independent and requires NADPH oxidase-derived superoxide, but not its dismutation product H2O2. To better define the biological regulation of CaMKII activation and signaling by Ang II, we evaluated the potential for peroxynitrite (ONOO(-)) to mediate CaMKII activation and downstream Kv4...
2016: Scientific Reports
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