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Hepatic angiotensin

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https://www.readbyqxmd.com/read/29136335/sii-ang-ii-potentiates-insulin-receptor-signalling-and-glycogen-synthesis-in-hepatocytes
#1
Samra Joke Sanni, Christina Lyngsø, Steen Gammeltoft, Jakob Lerche Hansen
The angiotensin II type I receptor (AT1R) is involved in the regulation of cardiovascular function. Excessive activation of AT1R by angiotensin II (Ang II) leads to cardiovascular disease and may be involved in the development of insulin resistance and diabetes. Functionally selective Ang II analogues, such as the [Sar1, Ile4, Ile8]-angiotensin II (SII Ang II) analogue that only activates a subset of signalling networks have been demonstrated to have beneficial effects on cardiovascular function in certain settings, including lowering blood pressure and increasing cardiac performance...
November 14, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29046730/aliskiren-effect-on-non-alcoholic-steatohepatitis-in-metabolic-syndrome
#2
F N Ramalho, S C Sanches, M C Foss, M J Augusto, D M Silva, A M Oliveira, L N Ramalho
BACKGROUND: Non-alcoholic steatohepatitis (NASH) is highly associated with metabolic syndrome, a major cause of morbidity in the globalized society. The renin-angiotensin system (RAS) influences hepatic fatty acid metabolism, inflammation and fibrosis. Thus, in the present study, we aimed to evaluate the effect of aliskiren, a direct renin inhibitor, on metabolic syndrome-related NASH. METHODS: C57BL/6 male mice (n = 45) were divided into three groups: controls; animals inoculated with streptozotocin (STZ) (40 mg/kg/day) for 5 days and fed with high fat diet (HFD) for 8 weeks; and animals inoculated with STZ for 5 days, fed with HFD for 8 weeks and treated with aliskiren (100 mg/kg/day) for the final 2 weeks...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/29029395/rasal1-is-a-potent-regulator-of-hepatic-stellate-cell-activity-and-liver-fibrosis
#3
Akemi Takata, Motoyuki Otsuka, Takahiro Kishikawa, Mari Yamagami, Rei Ishibashi, Kazuma Sekiba, Tatsunori Suzuki, Motoko Ohno, Yui Yamashita, Takaya Abe, Ryota Masuzaki, Tsuneo Ikenoue, Kazuhiko Koike
Liver fibrosis, leading to cirrhosis and liver failure, can occur after chronic liver injury. The transition of hepatic stellate cells (HSCs) from quiescent cells into proliferative and fibrogenic cells is a central event in liver fibrosis. Here, we show that RAS protein activator like-1 (RASAL1), a RAS-GTPase-activating protein, which switches off RAS activity, is significantly decreased during HSC activation, and that HSC activation can be antagonized by forced expression of the RASAL1 protein. We demonstrate that RASAL1 suppresses HSC proliferation by regulating the Ras-MAPK pathway, and that RASAL1 suppresses HSC fibrogenic activity by regulating the PKA-LKB1-AMPK-SRF pathway by interacting with angiotensin II receptor, type 1...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28953991/candesartan-rather-than-losartan-improves-motor-dysfunction-in-thioacetamide-induced-chronic-liver-failure-in-rats
#4
H A Murad, Z J Gazzaz, S S Ali, M S Ibraheem
Minimal hepatic encephalopathy is more common than the acute syndrome. Losartan, the first angiotensin-II receptor blocker (ARB), and candesartan, another widely-used ARB, have protected against developing fibrogenesis, but there is no clear data about their curative antifibrotic effects. The current study was designed to examine their effects in an already-established model of hepatic fibrosis and also their effects on the associated motor dysfunction. Low-grade chronic liver failure (CLF) was induced in 3-month old Sprague-Dawley male rats using thioacetamide (TAA, 50 mg·kg-1·day-1) intraperitoneally for 2 weeks...
September 21, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28886996/a-prodrug-design-for-improved-oral-absorption-and-reduced-hepatic-interaction
#5
Gulzar Ahmed, Walter Elger, Frederick Meece, Hareesh B Nair, Birgitt Schneider, Ralf Wyrwa, Klaus Nickisch
A series of estradiol-17-β esters of N-(p-sulfomylbenzamide)-amino acids were prepared and evaluated for systemic and hepatic estrogenic activity after oral administration in ovariectomized rats. The alkyl substitution at nitrogen of amino acids such as proline or N-methyl-alanine produced compounds that exhibit potent oral activity. The proline analog (EC508) was further evaluated along with 17β-estradiol (E2) and ethinyl-estradiol (EE) and compared their effects on the uterus, angiotensin and HDL-cholesterol after oral administration to ovariectomized female rats...
October 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28845018/loss-of-angiotensin-converting-enzyme-ii-ace2-accelerates-the-development-of-liver-injury-induced-by-thioacetamide
#6
Hsi-Tien Wu, Ya-Wen Chuang, Cheng-Pu Huang, Ming-Huang Chang
Angiotensin converting enzyme II (ACE2), an angiotensin converting enzyme (ACE) homologue that displays antagonist effects on ACE/angiotensin II (Ang II) axis in renin-angiotensin system (RAS), could play a protective role against liver damages. The purpose of this study is to investigate whether inflammation-mediated liver injury could be affected by ACE2 derived pathways in the RAS. Eight-weeks-old wild-type (WT; C57BL/6) and Ace2 KO (hemizygous Ace2(-/y)) male mice were used to induce liver fibrosis by thioacetamide (TAA) administration (0, 100, and 200 mg/kg BW)...
August 25, 2017: Experimental Animals
https://www.readbyqxmd.com/read/28841231/noncholestatic-acute-hepatocellular-injury-following-candesartan-administration
#7
Jan Antonio Lammel-Lindemann, Eduardo Flores-Villalba, Alexandro Jose Martagón, Eduardo DeObeso-Gonzalez, Francisco Puente-Gallegos
Arterial hypertension is a highly manageable disorder due to a variety of drugs available for its treatment. Since the late 1990s, angiotensin II receptor blockers have been widely prescribed, achieving appropriate control in patients' blood pressure. Few cases of serious adverse effects have been reported to date. Here, we present a case of acute hepatocellular injury secondary to candesartan administration. Further studies should be performed in patients who present with this adverse effect, in order to prevent more serious outcomes...
August 25, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28822808/bml-111-equilibrated-ace-angii-at1r-and-ace2-ang-1-7-mas-axis-to-protect-hepatic-fibrosis-in-rats
#8
Quandong Hu, Zhenzhen Hu, Qiongfeng Chen, Yonghong Huang, Zi Mao, Fangyun Xu, Xiaoyan Zhou
BACKGROUND: It was recently reported Lipoxins (LXs) had protective effects on fibrous diseases, and renin-angiotensin-aldosterone system (RAAS) had played vital and bidirectional roles in hepatic fibrosis. In this paper, a hepatic fibrosis model, induced by carbon tetrachloride (CCL4) in rats, was used to observe the relations between RAAS and LXs, as well as to further explore the alternative anti-fibrosis mechanisms of LXs. METHODS: The model was evaluated by morphological observations and biochemical assays...
August 16, 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28811860/the-apelin-receptor-apj-in-hematopoietic-stem-cells-progenitor-cells-in-the-early-stage-of-non-alcoholic-steatohepatitis
#9
Wataru Ando, Hiroaki Yokomori, Katsuya Otori, Masaya Oda
BACKGROUND: Non-alcoholic steatohepatitis (NASH) is characterized by hepatic steatosis and inflammation with or without fibrosis. The apelin receptor (APJ) is related to angiotensin-like-receptor 1 (AGTRL1). The present study aimed to evaluate APJ as an indicator of the pathophysiology of early-stage NASH. METHODS: APJ expression was evaluated in six tissue samples with histologically proven early-stage NASH using immunohistochemistry (IHC) and immunoelectron microscopy (IEM)...
September 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28798388/angiotensin-ii-induces-connective-tissue-growth-factor-expression-in-human-hepatic-stellate-cells-by-a-transforming-growth-factor-%C3%AE-independent-mechanism
#10
Ao Li, Jingyao Zhang, Xiaoxun Zhang, Jun Wang, Songsong Wang, Xiao Xiao, Rui Wang, Peng Li, Yitao Wang
Angiotensin II (Ang II) promotes hepatic fibrosis by increasing extracellular matrix (ECM) synthesis. Connective tissue growth factor (CTGF) plays a crucial role in the pathogenesis of hepatic fibrosis and emerges as downstream of the profibrogenic cytokine transforming growth factor-β (TGF-β). We aimed to investigate the molecular events that lead from the Ang II receptor to CTGF upregulation in human hepatic stellate cells, a principal fibrogenic cell type. Ang II produced an early, AT1 receptor-dependent stimulation of CTGF expression and induced a rapid activation of PKC and its downstream p38 MAPK, thereby activating a nuclear factor-κB (NF-κB) and Smad2/3 cross-talk pathway...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28792970/targeting-hepatic-heparin-binding-egf-like-growth-factor-hb-egf-induces-anti-hyperlipidemia-leading-to-reduction-of-angiotensin-ii-induced-aneurysm-development
#11
Seonwook Kim, Lihua Yang, Seongu Kim, Richard G Lee, Mark J Graham, Judith A Berliner, Aldons J Lusis, Lei Cai, Ryan E Temel, Debra L Rateri, Sangderk Lee
OBJECTIVE: The upregulated expression of heparin binding EGF-like growth factor (HB-EGF) in the vessel and circulation is associated with risk of cardiovascular disease. In this study, we tested the effects of HB-EGF targeting using HB-EGF-specific antisense oligonucleotide (ASO) on the development of aortic aneurysm in a mouse aneurysm model. APPROACH AND RESULTS: Low-density lipoprotein receptor (LDLR) deficient mice (male, 16 weeks of age) were injected with control and HB-EGF ASOs for 10 weeks...
2017: PloS One
https://www.readbyqxmd.com/read/28761237/membranoproliferative-glomerulonephritis-associated-with-a-human-immunodeficiency-virus-infection
#12
H Rafik, M El Amrani, D El Kabbaj
Type 1 membranoproliferative glomerulonephritis (MPGN) is an uncommon manifestation of human immunodeficiency virus (HIV)-associated renal disease in patients coinfected with hepatitis C virus. We report a case of MPGN characterized by nephrotic syndrome associated with HIV without hepatitis C coinfection. The patient had a favorable response to highly active antiretroviral therapy and angiotensin-converting enzyme inhibitors. Recognition of the MPGN lesion in HIV infection devoid of hepatitis C coinfection must be considered...
July 2017: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/28750149/single-center-evaluation-of-the-pharmacokinetics-and-safety-of-the-angiotensin-ii-receptor-antagonist-azilsartan-medoxomil-in-mild-to-moderate-hepatic-impairment
#13
Caroline Dudkowski, Aziz Karim, Zhen Zhao, Alberto B Alonso, Dyal Garg, Richard A Preston
Azilsartan medoxomil (AZL-M) is a potent angiotensin II receptor blocker that decreases blood pressure in a dose-dependent manner. It is a prodrug that is not detected in blood after its oral administration because of its rapid hydrolysis to the active moiety, azilsartan (AZL). AZL undergoes further metabolism to the major metabolite, M-II, and minor metabolites. The objective of this study was to determine the effect of mild to moderate hepatic impairment on the pharmacokinetics of AZL and its major metabolite...
July 27, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28740597/is-hepatic-steatosis-associated-with-left-ventricular-mass-index-increase-in-the-general-population
#14
Katharina Piontek, Carsten O Schmidt, Sebastian E Baumeister, Markus M Lerch, Julia Mayerle, Marcus Dörr, Stephan B Felix, Henry Völzke
AIM: To investigate the association between hepatic steatosis and change in left ventricular mass index (LVMI) over five years, and examine whether systolic and diastolic blood pressures are mediators of the association between hepatic steatosis and LVMI using a general population sample. METHODS: We analyzed data from the Study of Health in Pomerania. The study population comprised 1298 individuals aged 45 to 81 years. Hepatic steatosis was defined as the presence of a hyperechogenic pattern of the liver together with elevated serum alanine transferase levels...
July 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28691216/statins-and-ace-inhibitors-are-associated-with-reduced-mortality-and-morbidity-in-chronic-liver-disease
#15
Knut Stokkeland, Christine Takami Lageborn, Anders Ekbom, Jonas Höijer, Matteo Bottai, Per Stål, Karin Söderberg-Löfdal
Liver fibrosis is a common response to many chronic liver diseases. The aim of our study was to explore whether pharmacotherapy for concurrent diseases affects overall mortality, liver-related mortality and liver-related morbidity in patients with chronic liver disease. We performed a register-based cohort study of all patients with a first-time diagnosis of chronic liver disease between 2005 and 2012 in Sweden (n=70 546). Data from the Patient Register, the Prescribed Drug Register and the Death Certificate Register were linked...
July 10, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28660748/angiotensin-ii-subtype-1a-receptor-signaling-in-resident-hepatic-macrophages-induces-liver-metastasis-formation
#16
Yuki Shimizu, Hideki Amano, Yoshiya Ito, Tomohiro Betto, Sakiko Yamane, Tomoyoshi Inoue, Nobuyuki Nishizawa, Yoshio Matsui, Mariko Kamata, Masaki Nakamura, Hidero Kitasato, Wasaburo Koizumi, Masataka Majima
Liver metastases from colorectal cancer (CRC) are a clinically significant problem. The renin-angiotensin system is involved in tumor growth and metastases. This study was designed to evaluate the role of angiotensin II subtype receptor 1a (AT1a) in the formation of liver metastasis in CRC. A model of liver metastasis was developed by intrasplenic injection of mouse colon cancer (CMT-93) into AT1a knockout mice (AT1aKO) and wild-type (C57BL/6) mice (WT). Compared with WT mice, the liver weight and liver metastatic rate were significantly lower in AT1aKO...
September 2017: Cancer Science
https://www.readbyqxmd.com/read/28660012/angiotensin-ii-or-epinephrine-hemodynamic-and-metabolic-responses-in-the-liver-of-l-name-induced-hypertension-and-spontaneous-hypertensive-rats
#17
Debora Conte Kimura, Marcia Regina Nagaoka, Durval Rosa Borges, Maria Kouyoumdjian
AIM: To study hepatic vasoconstriction and glucose release induced by angiotensin (Ang)II or Epi in rats with pharmacological hypertension and spontaneously hypertensive rat (SHR). METHODS: Isolated liver perfusion was performed following portal vein and vena cava cannulation; AngII or epinephrine (Epi) was injected in bolus and portal pressure monitored; glucose release was measured in perfusate aliquots. RESULTS: The portal hypertensive response (PHR) and the glucose release induced by AngII of L-NAME were similar to normal rats (WIS)...
June 18, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28629818/corydalis-hendersonii-hemsl-protects-against-myocardial-injury-by-attenuating-inflammation-and-fibrosis-via-nf-%C3%AE%C2%BAb-and-jak2-stat3-signaling-pathways
#18
Ruifeng Bai, Xu Yin, Xiao Feng, Yuan Cao, Yan Wu, Zhixiang Zhu, Chun Li, Pengfei Tu, Xingyun Chai
ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis hendersonii Hemsl. (CH) with heat clearing and detoxifying effects are well described in Tibetan folk medicine. It has been used for centuries in China largely for the treatment of high altitude polycythemia, a pathophysiological condition referred to "plethora" in Tibetan medicine, hypertension, hepatitis, edema, gastritis, and other infectious diseases. AIM OF THE STUDY: To investigate the cardioprotective effects of Corydalis hendersonii extract in an ICR mouse model of myocardial ischemic injury...
June 16, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28626963/exercise-training-modulates-the-hepatic-renin-angiotensin-system-in-fructose-fed-rats
#19
Eliete Dalla Corte Frantz, Renata Frauches Medeiros, Isabele Gomes Giori, Juliana Bittencourt Silveira Lima, Thais Bento-Bernardes, Thaiane Gadioli Gaique, Caroline Fernandes-Santos, Tiago Fernandes, Edilamar Menezes Oliveira, Carla Paulo Vieira, Carlos Adam Conte-Junior, Karen Jesus Oliveira, Antonio Claudio Lucas Nobrega
What is the central question of this study? What are the effects of exercise training on the hepatic renin-angiotensin system and their contribution to damage resulting from fructose overload in rats? What is the main finding and its importance? Exercise training attenuated the deleterious actions of the angiotensin-converting enzyme/angiotensin II/angiotensin II type 1 receptor axis and increased expression of the counter-regulatory (angiotensin-converting enzyme 2/angiotensin (1-7)/Mas receptor) axis in the liver...
June 19, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28596676/renin-angiotensin-system-in-liver-diseases-friend-or-foe
#20
REVIEW
Ana Cristina Simões E Silva, Aline S Miranda, Natália P Rocha, Antônio L Teixeira
In the last three decades, the understanding of the renin angiotensin system (RAS) has been changed by the discoveries of functional local systems, novel biologically active peptides, additional specific receptors, alternative pathways of angiotensin (Ang) II generation, and new roles for enzymes and precursor components other than those in Ang II synthesis. In this regard, the discovery that Ang-(1-7) opposes the pressor, proliferative, pro-fibrotic, and pro-inflammatory effects mediated by Ang II has contributed to the realization that the RAS is composed of two axes...
May 21, 2017: World Journal of Gastroenterology: WJG
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