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Angiotensin II stimulates endothelin

Mark W Cunningham, Javier Castillo, Tarek Ibrahim, Denise C Cornelius, Nathan Campbell, Lorena Amaral, Venkata Ramana Vaka, Nathan Usry, Jan M Williams, Babbette LaMarca
Women with preeclampsia produce AT1-AA (agonistic autoantibodies to the angiotensin II type 1 receptor), which stimulate reactive oxygen species, inflammatory factors, and hypertensive mechanisms (ET [endothelin] and sFlt-1 [soluble fms-like tyrosine kinase-1]) in rodent models of preeclampsia. The placental ischemic reduced uterine perfusion pressure (RUPP) rat model of preeclampsia exhibits many of these features. In this study, we examined the maternal outcomes of AT1-AA inhibition ('n7AAc') in RUPP rats...
March 19, 2018: Hypertension
Colin A Nurse, Erin M Leonard, Shaima Salman
Mammalian carotid bodies (CB) are chemosensory organs that mediate compensatory cardiorespiratory reflexes in response to low blood PO2 (hypoxemia) and elevated CO2 /H+ (acid hypercapnia). The chemoreceptors are glomus or type I cells which occur in clusters enveloped by neighboring glial-like type II cells. During chemoexcitation type I cells depolarize, leading to Ca2+ -dependent release of several neurotransmitters, some excitatory and others inhibitory, which help shape the afferent carotid sinus nerve (CSN) discharge...
March 9, 2018: Physiological Genomics
Shalini Jamwal, Saurabh Sharma
AIM: Vascular endothelium plays a role in capillary transport of nutrients and drugs and regulates angiogenesis, homeostasis, as well as vascular tone and permeability as a major regulator of local vascular homeostasis. The present study has been designed to investigate the role of endothelium in metabolic disorders. METHODS: The endothelium maintains the balance between vasodilatation and vasoconstriction, procoagulant and anticoagulant, prothrombotic and antithrombotic mechanisms...
January 25, 2018: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Francesca Schinzari, Manfredi Tesauro, Augusto Veneziani, Nadia Mores, Nicola Di Daniele, Carmine Cardillo
Obese patients have vascular dysfunction related to impaired insulin-stimulated vasodilation and increased endothelin-1-mediated vasoconstriction. In contrast to the harmful vascular actions of angiotensin (Ang) II, the angiotensin-converting enzyme 2 product Ang-(1-7) has shown to exert cardiovascular and metabolic benefits in experimental models through stimulation of the Mas receptor. We, therefore, examined the effects of exogenous Ang-(1-7) on vasodilator tone and endothelin-1-dependent vasoconstriction in obese patients...
January 2018: Hypertension
Alexandre Beautrait, Justine S Paradis, Brandon Zimmerman, Jenna Giubilaro, Ljiljana Nikolajev, Sylvain Armando, Hiroyuki Kobayashi, Lama Yamani, Yoon Namkung, Franziska M Heydenreich, Etienne Khoury, Martin Audet, Philippe P Roux, Dmitry B Veprintsev, Stéphane A Laporte, Michel Bouvier
In addition to G protein-coupled receptor (GPCR) desensitization and endocytosis, β-arrestin recruitment to ligand-stimulated GPCRs promotes non-canonical signalling cascades. Distinguishing the respective contributions of β-arrestin recruitment to the receptor and β-arrestin-promoted endocytosis in propagating receptor signalling has been limited by the lack of selective analytical tools. Here, using a combination of virtual screening and cell-based assays, we have identified a small molecule that selectively inhibits the interaction between β-arrestin and the β2-adaptin subunit of the clathrin adaptor protein AP2 without interfering with the formation of receptor/β-arrestin complexes...
April 18, 2017: Nature Communications
Francesca Schinzari, Augusto Veneziani, Nadia Mores, Angela Barini, Nicola Di Daniele, Carmine Cardillo, Manfredi Tesauro
Patients with central obesity have impaired insulin-stimulated vasodilation and increased ET-1 (endothelin 1) vasoconstriction, which may contribute to insulin resistance and vascular damage. Apelin enhances insulin sensitivity and glucose disposal but also acts as a nitric oxide (NO)-dependent vasodilator and a counter-regulator of AT1 (angiotensin [Ang] II type 1) receptor-induced vasoconstriction. We, therefore, examined the effects of exogenous (Pyr(1))apelin on NO-mediated vasodilation and Ang II- or ET-1-dependent vasoconstrictor tone in obese patients...
May 2017: Hypertension
Yan Lu, Xudong Zhu, Jinjie Li, Ru Fang, Zhuoyun Wang, Jing Zhang, Kexue Li, Xiaoyu Li, Hui Bai, Qing Yang, Jingjing Ben, Hanwen Zhang, Qi Chen
As a major amino acid, glycine has multiple functions in metabolism, growth, immunity, cytoprotection, and survival. The aim of this study was to determine the effects of glycine on pathologic cardiac hypertrophy and the mechanism underlying it. Pre-treatment with glycine significantly attenuated murine cardiac hypertrophy induced by transverse aortic constriction or by administration of angiotensin II (Ang II). This action was associated with a suppressive extracellular signal-regulated kinase 1/2 phosphorylation in myocardium...
January 1, 2017: Biochemical Pharmacology
Heng-Jing Hu, Zhi-Sheng Jiang, Sheng-Hua Zhou, Qi-Ming Liu
The effects of hydrogen sulfide (H2S) and the nuclear factor κB (NF-κB) signaling pathway in angiotensin II (AngII)-induced endothelin-1 (ET-1) expression and subsequent cytotoxicity remain unclear. The present study aimed to investigate the hypothesis that H2S protects human umbilical vein endothelial cells (HUVECs) against AngII‑stimulated ET‑1 generation and subsequent cytotoxicity‑induced endoplasmic reticulum stress via the NF‑κB signaling pathway. The results of the present study demonstrated that AngII significantly upregulated the expression levels of ET‑1, glucose‑regulated protein 78, CCAAT‑enhancer‑binding protein homologous protein, phosphorylated (p)‑p65 and inducible nitric oxide synthase; stimulated nitric oxide production; suppressed the expression and activity of cystathionine-γ-lyase (CSE), a H2S synthetase; and decreased cell viability...
November 2016: Molecular Medicine Reports
Ze-Jun Huo, Dong Li, Jia Guo, Sai Li, Ning Ding, Zhi-Xin Li
OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation on the expressions of angiotensinogen (AGT), angiotensin II type 1 receptor (AT1R), endothelin-1 (ET1), and endothelin A receptor (ETAR) mRNA in spontaneously hypertensive rat (SHR) aorta. METHODS: Eighteen male SHRs were randomly divided into three groups, an SHR group, an SHR Baihui (DU 20) and Zusanli (ST 36) acupoint (SHR-AP) group, and an SHR non-acupoint (SHR-NAP) group, with 6 rats in each group...
October 2016: Chinese Journal of Integrative Medicine
Zhong Zhang, Kristie Payne, Thomas L Pallone
Using dual-cell electrophysiological recording, we examined the routes for equilibration of membrane potential between the pericytes and endothelia that comprise the descending vasa recta (DVR) wall. We measured equilibration between pericytes in intact vessels, between pericytes and endothelium in intact vessels and between pericytes physically separated from the endothelium. Dual pericyte recording on the abluminal surface of DVR showed that both resting potential and subsequent time-dependent voltage fluctuations after vasoconstrictor stimulation remained closely equilibrated, regardless of the agonist employed (angiotensin II, vasopressin or endothelin 1)...
2016: PloS One
Ying Gao, Jian Yang, Shu Wang
OBJECTIVE: This study aimed to investigate the effects of radio-telemetry implantation surgery on blood pressure (BP) and renin-angiotensin-aldosterone system (RAAS), calcitonin gene-related peptide (CGRP) and endothelin-1 (ET-1) in rats. METHODS: Six spontaneously hypertensive rat (SHRs) and six WKY rats successfully implanted telemetry were used as experimental group, while six SHRs and six Wistar-Kyoto (WKY) rats of comparable age, weight and BP free from implantation surgery were used as normal control group...
2016: Clinical and Experimental Hypertension: CHE
Otavio Cabral-Marques, Gabriela Riemekasten
Systemic sclerosis (SSc) is a connective tissue disorder of unknown etiology characterized by the presence of multiple autoantibodies, including those against angiotensin and endothelin receptors. Patients with SSc can develop heterogeneous clinical manifestations including microvascular damage, the dysregulation of innate and adaptive immunity, and generalized fibrosis of multiple organs. Autoantibodies against angiotensin II type I receptor (AT1R) and endothelin-1 type A receptor (ETAR) play important roles in the pathogenesis of SSc...
July 2016: Autoimmunity Reviews
Vanesa D Ramseyer, Pablo A Ortiz, Oscar A Carretero, Jeffrey L Garvin
In thick ascending limbs (THALs), nitric oxide (NO) decreases NaCl reabsorption via cGMP-mediated inhibition of Na-K-2Cl cotransporter (NKCC2). In angiotensin (ANG II)-induced hypertension, endothelin-1 (ET-1)-induced NO production by THALs is impaired. However, whether this alters NO's natriuretic effects and the mechanisms involved are unknown. In other cell types, ANG II augments phosphodiesterase 5 (PDE5)-mediated cGMP degradation. We hypothesized that NO-mediated inhibition of NKCC2 activity and stimulation of cGMP synthesis are blunted via PDE5 in ANG II-induced hypertension...
April 15, 2016: American Journal of Physiology. Renal Physiology
Judith Rademacher, Angela Kill, Kathrin Mattat, Duska Dragun, Elise Siegert, Jeannine Günther, Gabriela Riemekasten
OBJECTIVE: To assess monocytic expression and ratio of angiotensin and endothelin receptors in systemic sclerosis (SSc) and their functional relevance. METHODS: Receptor expression was measured by flow cytometry. Chemokine ligand 18 (CCL18) concentration in supernatants of peripheral blood mononuclear cells stimulated with immunoglobulin G was measured by ELISA. RESULTS: Monocytes of patients with SSc presented an increased angiotensin II Type 1 receptor (AT1R)/AT2R ratio compared with those of healthy donors...
March 2016: Journal of Rheumatology
Sören Otto, Andreas Deussen, Birgit Zatschler, Bianca Müller, Anja Neisser, Kathrin Barth, Henning Morawietz, Irakli Kopaliani
AIMS: Aortic stiffness is an independent risk factor for progression of cardiovascular diseases. Degradation of elastic fibres in aorta due to angiotensin II (ANGII)-stimulated overactivation of latent membrane type 1 matrix metalloproteinase (MT1MMP) and matrix metalloproteinase-2 (MMP2) is regarded to represent an important cause of aortic stiffness. Therefore, clarification of the causal mechanisms triggering the overactivation of these MMPs is of utmost importance. This study addresses the endothelium as a novel key activator of latent pro-MT1MMP and pro-MMP2 in rat aorta...
March 1, 2016: Cardiovascular Research
Linmao Lyu, Hui Wang, Bin Li, Qingyun Qin, Lei Qi, Mitzi Nagarkatti, Prakash Nagarkatti, Joseph S Janicki, Xing Li Wang, Taixing Cui
Chronic activation of the myocardial renin angiotensin system (RAS) elevates the local level of angiotensin II (Ang II) thereby inducing pathological cardiac hypertrophy, which contributes to heart failure. However, the precise underlying mechanisms have not been fully delineated. Herein we report a novel paracrine mechanism between cardiac fibroblasts (CF)s and cardiomyocytes whereby Ang II induces pathological cardiac hypertrophy. In cultured CFs, Ang II treatment enhanced exosome release via the activation of Ang II receptor types 1 (AT1R) and 2 (AT2R), whereas lipopolysaccharide, insulin, endothelin (ET)-1, transforming growth factor beta (TGFβ)1 or hydrogen peroxide did not...
December 2015: Journal of Molecular and Cellular Cardiology
Renna Luo, Weiru Zhang, Cheng Zhao, Yujin Zhang, Hongyu Wu, Jianping Jin, Wenzheng Zhang, Almut Grenz, Holger K Eltzschig, Lijian Tao, Rodney E Kellems, Yang Xia
Hypertensive chronic kidney disease is one of the most prevalent medical conditions with high morbidity and mortality in the United States and worldwide. However, early events initiating the progression to hypertensive chronic kidney disease are poorly understood. We hypothesized that elevated endothelial hypoxia-inducible factor-1α (HIF-1α) is a common early insult triggering initial glomerular injury leading to hypertensive chronic kidney disease. To test our hypothesis, we used an angiotensin II infusion model of hypertensive chronic kidney disease to determine the specific cell type and mechanisms responsible for elevation of HIF-1α and its role in the progression of hypertensive chronic kidney disease...
July 2015: Hypertension
F J Villarreal, N N Kim
The cardiac fibroblast is numerically the most abundant cell in the myocardium and is responsible for the deposition of the extracellular matrix (ECM). The cardiac ECM is a hierarchical, three-dimensional network in the heart, of which fibrillar collagens types I and III are the major structural components. Normal and pathological deposition of fibrillar collagen in the heart appears to rely on the regulation of ECM components such as fibronectin. Many humoral mediators have been noted to modulate the function of cardiac fibroblasts...
May 1998: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
Liming Yu, Guang Yang, Xinyu Weng, Peng Liang, Luyang Li, Jianfei Li, Zhiwen Fan, Wenfang Tian, Xiaoyan Wu, Huihui Xu, Minming Fang, Yong Ji, Yuehua Li, Qi Chen, Yong Xu
OBJECTIVE: Endothelin-1 is a potent vasoconstrictor derived from vascular endothelium. Elevated endothelin-1 levels are observed in a host of cardiovascular pathologies including cardiomyopathy. The epigenetic mechanism responsible for endothelin-1 induction in these pathological processes remains elusive. APPROACH AND RESULTS: We report here that induction of endothelin-1 expression in endothelial cells by angiotensin II (Ang II) was accompanied by the accumulation of histone H3K4 trimethylation, a preeminent histone modification for transcriptional activation, on the endothelin-1 promoter...
May 2015: Arteriosclerosis, Thrombosis, and Vascular Biology
Sheng Jun An, Pei Liu, Tie Mei Shao, Zhi Jun Wang, Hai Gang Lu, Zhan Jiao, Xue Li, Jun Qiu Fu
BACKGROUND: Adventitial fibroblasts have been shown to play an important role in vascular remodeling and contribute to neointimal formation in vascular diseases. However, little is known about adventitial fibroblast subpopulations. This study explored the process of isolating rat thoracic aorta adventitial fibroblast subpopulations and characterized their properties following stimulation with angiotensin II (ANG II), a critical factor involved in cardiovascular diseases such as hypertension...
2015: Cellular Physiology and Biochemistry
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