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https://www.readbyqxmd.com/read/27911784/%C3%AE-arrestin-mediates-the-frank-starling-mechanism-of-cardiac-contractility
#1
Dennis M Abraham, Robert T Davis, Chad M Warren, Lan Mao, Beata M Wolska, R John Solaro, Howard A Rockman
The Frank-Starling law of the heart is a physiological phenomenon that describes an intrinsic property of heart muscle in which increased cardiac filling leads to enhanced cardiac contractility. Identified more than a century ago, the Frank-Starling relationship is currently known to involve length-dependent enhancement of cardiac myofilament Ca(2+) sensitivity. However, the upstream molecular events that link cellular stretch to the length-dependent myofilament Ca(2+) sensitivity are poorly understood. Because the angiotensin II type 1 receptor (AT1R) and the multifunctional transducer protein β-arrestin have been shown to mediate mechanosensitive cellular signaling, we tested the hypothesis that these two proteins are involved in the Frank-Starling mechanism of the heart...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27905143/characterization-of-adverse-drug-reactions-causing-admission-to-an-intensive-care-unit
#2
Camilo Rojas-Velandia, Jair Ruiz-Garzón, Juan-Carlos Moscoso-Alcina, Álvaro Vallejos-Narvaéz, Jenny Castro-Canoa, Yuri Bustos-Martínez, Max Flórez-Cutiva, Mabel Contreras-Muñoz, Jully-Carolina Gómez-Gil, Carlos-Alberto Calderón-Ospina
AIM: This study aimed to determine the occurrence of adverse drug reactions (ADRs) that caused admission to the intensive care unit (ICU) of a university hospital. METHODS: Clinical records were reviewed for patients meeting the inclusion criteria who were admitted to the ICU between September and December 2012. Suspected cases of adverse drug reactions (ADR) were documented. Nine researchers later evaluated causality using the Naranjo Algorithm, preventability using the Schumock and Thornton criteria, and clinical classification based on the dose-time-susceptibility (DoTS) system...
December 1, 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27903643/effects-of-antihypertensive-agents-on-intestinal-contractility-in-the-spontaneously-hypertensive-rat-angiotensin-receptor-system-down-regulation-by-losartan
#3
Glen S Patten, Mahinda Y Abeywardena
Hypertension is an inflammatory condition controlled by the renin angiotensin system and is linked to kidney disease, diabetes mellitus and recently to dysfunction of the gut. The aim of this study was to determine what effect anti-hypertensive drug treatments may have on intestinal function of the spontaneously hypertensive rat (SHR). In the first experiment SHR were treated with enalapril or hydralazine. In the second experiment SHR were treated with losartan with no-treatment as control for both experiments...
November 30, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27884084/losartan-loaded-liposomes-improve-the-antitumor-efficacy-of-liposomal-paclitaxel-modified-with-ph-sensitive-peptides-by-inhibition-of-collagen-in-breast-cancer
#4
Tai Xia, Qin He, Kairong Shi, Yang Wang, Qianwen Yu, Li Zhang, Qianyu Zhang, Huile Gao, Lifang Ma, Ji Liu
The dense collagen network in tumors restricts the penetration of drugs into tumors. Free losartan could inhibit collagen, but it would cause hypotension at the dosage of 10 mg/kg/d. In this study, losartan was encapsulated in liposomes (LST-Lip) and the collagen inhibition ability of LST-Lip was investigated. Our results showed the blood pressure was not affected by LST-Lip at the dosage of 2.5 mg/kg every other day. The amount of Evans Blue in tumor in LST-Lip group was 1.98 times of that in control group...
November 25, 2016: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/27881877/exercise-training-attenuates-renovascular-hypertension-partly-via-ras-ros-glutamate-pathway-in-the-hypothalamic-paraventricular-nucleus
#5
Yan Zhang, Xiao-Jing Yu, Wen-Sheng Chen, Hong-Li Gao, Kai-Li Liu, Xiao-Lian Shi, Xiao-Yan Fan, Lin-Lin Jia, Wei Cui, Guo-Qing Zhu, Jin-Jun Liu, Yu-Ming Kang
Exercise training (ExT) has been reported to benefit hypertension; however, the exact mechanisms involved are unclear. We hypothesized that ExT attenuates hypertension, in part, through the renin-angiotensin system (RAS), reactive oxygen species (ROS), and glutamate in the paraventricular nucleus (PVN). Two-kidney, one-clip (2K1C) renovascular hypertensive rats were assigned to sedentary (Sed) or treadmill running groups for eight weeks. Dizocilpine (MK801), a glutamate receptor blocker, or losartan (Los), an angiotensin II type1 receptor (AT1-R) blocker, were microinjected into the PVN at the end of the experiment...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27864612/secretory-products-from-epicardial-adipose-tissue-from-patients-with-type-2-diabetes-impair-mitochondrial-%C3%AE-oxidation-in-cardiomyocytes-via-activation-of-the-cardiac-renin-angiotensin-system-and-induction-of-mir-208a
#6
Marcel Blumensatt, Pia Fahlbusch, Rebecca Hilgers, Marlies Bekaert, Daniella Herzfeld de Wiza, Payam Akhyari, Johannes B Ruige, D Margriet Ouwens
Secretory products from epicardial adipose tissue (EAT) from patients with type 2 diabetes (T2D) impair cardiomyocyte function. These changes associate with alterations in miRNA expression, including the induction of miR-208a. Recent studies suggest that activation of the cardiac-specific renin-angiotensin system (RAS) may affect cardiac energy metabolism via induction of miR-208a. This study investigated whether cardiomyocyte dysfunction induced by conditioned media (CM) from EAT-T2D involves activation of the RAS/miR-208a pathway...
January 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/27853186/activated-hepatic-stellate-cells-play-pivotal-roles-in-hepatocellular-carcinoma-cell-chemoresistance-and-migration-in-multicellular-tumor-spheroids
#7
Yeonhwa Song, Se-Hyuk Kim, Kang Mo Kim, Eun Kyung Choi, Joon Kim, Haeng Ran Seo
Most Hepatocellular carcinoma (HCC) are resistant to conventional chemotherapeutic agents and remain an unmet medical need. Recently, multiple studies on the crosstalk between HCC and their tumor microenvironment have been conducted to overcome chemoresistance in HCC. In this study, we formed multicellular tumor spheroids (MCTS) to elucidate the mechanisms of environment-mediated chemoresistance in HCC. We observed that hepatic stellate cells (HSCs) in MCTS significantly increased the compactness of spheroids and exhibited strong resistance to sorafenib and cisplatin relative to other types of stromal cells...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27852609/il-17-mediates-neutrophil-infiltration-and-renal-fibrosis-following-recovery-from-ischemia-reperfusion-compensatory-role-of-natural-killer-cells-in-athymic-rats
#8
Purvi Mehrotra, Jason A Collett, Seth McKinney, Jackson Stevens, Carlie M Ivancic, David P Basile
T cells have been implicated in the pathogenesis of AKI as well as its progression to CKD. Previous studies suggest that Th17 cells participates during the AKI to CKD transition and inhibition of T cell activity by mycophenolate mofetil (MMF) or losartan attenuates the development of fibrosis following AKI. We hypothesized that T cell deficient rats may have reduced levels of IL-17 cytokine leading to decreased fibrosis following AKI. Renal I/R was performed on T cell deficient athymic rats (Foxn1rnu-/rnu-) and control euthymic rats (Foxn1rnu-/+) and CKD progression was hastened by unilateral nephrectomy at Day 33 and subsequent exposure to 4...
November 16, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27824157/effect-of-p22phox-depletion-on-sympathetic-regulation-of-blood-pressure-in-shrsp-evaluation-in-a-new-congenic-strain
#9
Hasan M Zahid, Mohammed Zubaerul Ferdaus, Hiroki Ohara, Minoru Isomura, Toru Nabika
Oxidative stress in the rostral ventrolateral medulla (RVLM), a sympathetic center in the brainstem, was implicated in the regulation of sympathetic activity in various hypertensive models including stroke-prone spontaneously hypertensive rats (SHRSP). In this study, we evaluated the role of the NADPH oxidases (NOX) in the blood pressure (BP) regulation in RVLM in SHRSP. The P22PHOX-depleted congenic SHRSP (called SP.MES) was constructed by introducing the mutated p22phox gene of Matsumoto Eosinophilic Shinshu rat...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27821539/endothelial-microparticles-from-acute-coronary-syndrome-patients-induce-premature-coronary-artery-endothelial-cells-ageing-and-thrombogenicity-role-of-the-ang-ii-at1-receptor-nadph-oxidase-mediated-activation-of-mapks-and-pi3-kinase-pathways
#10
Malak Abbas, Laurence Jesel, Cyril Auger, Lamia K Amoura, Nathan Messas, Guillaume Manin, Cordula Rumig, Antonio J León-González, Thais P Ribeiro, Grazielle C Silva, Raghida Abou-Merhi, Eva Hamade, Markus Hecker, Yannick Georg, Nabil Chakfe, Patrick Ohlmann, Valérie B Schini-Kerth, Florence Toti, Olivier Morel
BACKGROUND: -Microparticles (MPs) have emerged as a surrogate marker of endothelial dysfunction and cardiovascular risk. This study examined the potential of MPs from senescent endothelial cells (ECs) or from patients with acute coronary syndrome (ACS) to promote premature ECs ageing and thrombogenicity. METHODS: -Primary porcine coronary ECs were isolated from the left circumflex coronary artery. MPs were prepared from ECs and venous blood from patients with ACS (n=30) and from healthy volunteers (n=6) by sequential centrifugation...
November 7, 2016: Circulation
https://www.readbyqxmd.com/read/27820727/the-role-of-brain-angiotensin-ii-type-2-receptors-and-nitric-oxide-in-the-renal-sympathoinhibitory-response-to-acute-volume-expansion-in-conscious-rats
#11
Mohammed H Abdulla, Edward J Johns
OBJECTIVE: The study was performed to investigate the role of angiotensin II type 2 (AT2) receptors and nitric oxide in the renal sympathoinhibitory response to volume expansion (VEP). METHOD: Conscious rats were subjected to volume expansion (VEP) [0.25% body weight/min saline for 10 min intravenously (i.v.)] following intracerebroventricular (i.c.v.) infusion of either saline or angiotensin II (Ang II), or a combination of Ang II with either losartan, PD123319, or N-nitro-L-arginine methyl ester (L-NAME)...
November 4, 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27818251/mesoporous-silica-nanoparticles-as-a-new-carrier-methodology-in-the-controlled-release-of-the-active-components-in-a-polypill
#12
Antonio L Doadrio, José M Sánchez-Montero, Juan C Doadrio, Antonio J Salinas, María Vallet-Regí
Polypill is a medication designed for preventing heart attacks through a combination of drugs. Current formulations contain blood pressure-lowering drugs and others, such statins or acetylsalicylic acid. These drugs exhibit different physical chemical features, and consequently different release kinetics. Therefore, the concentration in plasma of some of them after the release process can be out of the therapeutic range. This paper investigates a new methodology for the control dosage of a polypill recently reported containing hydrochlorothiazide, amlodipine, losartan and simvastatin in a 12...
November 3, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27818235/high-sucrose-intake-during-gestation-increases-angiotensin-ii-type-1-receptor-mediated-vascular-contractility-associated-with-epigenetic-alterations-in-aged-offspring-rats
#13
Lei Wu, Aiping Shi, Di Zhu, Le Bo, Yuan Zhong, Juan Wang, Zhice Xu, Caiping Mao
Accruing evidence have confirmed that the fetal programming in response to adverse environmental in utero factors plays essential roles in the pathogenesis of hypertension in later life. High sugar intake has been accepted worldwide in everyday life diet and becomes the critical public health issue. Our previous studies indicated that intake of high sucrose (HS) during pregnancy could change the vascular reactivity and dipsogenic behavior closely associated with abnormal renin-angiotensin system (RAS), to increase the risk of hypertension in adult offspring...
December 2016: Peptides
https://www.readbyqxmd.com/read/27812496/reversible-exacerbation-of-obstructive-sleep-apnea-by-%C3%AE-1-adrenergic-blockade-with-tamsulosin-a-case-report
#14
Mark Moran
: Obstructive sleep apnea (OSA) is characterized by repeated involuntary closure of the pharyngeal airspace during sleep. Normal activity of the genioglossus (GG) muscle is important in maintaining airway patency, and inhibition of GG activity can contribute to airway closure. Neurons in the hypoglossal motor nucleus (HMN) regulate GG activity. Adrenergic tone is an important regulator of HMN neuronal excitability. In laboratory models α1-adrenergic antagonists inhibit HMN neurons and GG activity, suggesting that α1-adrenergic antagonism might adversely affect patients with OSA...
2016: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/27798124/cross-talk-between-amp-activated-protein-kinase-and-renin-angiotensin-system-in-uninephrectomised-rats
#15
Ke-Ke Yang, Yi Sui, Hui-Rong Zhou, Jian Shen, Ning Tan, Yan-Mei Huang, Sha-Sha Li, Yan-Hong Pan, Xiao-Xi Zhang, Hai-Lu Zhao
INTRODUCTION: The renal renin-angiotensin system (RAS) and the ultrasensitive energy sensor AMP-activated protein kinase (AMPK) have been implicated in normal and aberrant states of the kidney, but interaction between the RAS and AMPK remains unknown. METHODS: Ninety-six rats were stratified into four groups: sham, uninephrectomised, uninephrectomised rats treated with the angiotensin-converting enzyme inhibitor lisinopril or the angiotensin receptor blocker losartan...
October 2016: Journal of the Renin-angiotensin-aldosterone System: JRAAS
https://www.readbyqxmd.com/read/27798092/igf-1-gh-axis-enhances-losartan-treatment-in-lama2-related-muscular-dystrophy
#16
Anthony Accorsi, Ajay Kumar, Younghwa Rhee, Alex Miller, Mahasweta Girgenrath
As the complexities of dystrophic pathology have been elucidated over the last few years, it has become increasingly clear that primary monogenetic defects result in multiple secondary pathologies capable of autonomously driving disease progression. Consequently, single-mode therapies fail to comprehensively ameliorate all aspects of pathology. Lama2-related muscular dystrophy (MDC1A) is a devastating congenital muscular dystrophy caused by mutations in the LAMA2 gene that results in multi-faceted secondary pathologies that include inflammation, fibrosis, apoptosis, and necrosis leading to severe muscle weakness and minimal postnatal growth...
October 24, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27780713/differential-effects-of-angiotensin-receptor-blockers-on-pancreatic-islet-remodelling-and-glucose-homeostasis-in-diet-induced-obese-mice
#17
Francielle Graus-Nunes, Thatiany de Souza Marinho, Sandra Barbosa-da-Silva, Marcia Barbosa Aguila, Carlos Alberto Mandarim-de-Lacerda, Vanessa Souza-Mello
Obesity leads to adverse endocrine pancreas remodelling, reduced islet lifespan and early type 2 diabetes onset. AT1R blockade shows beneficial pleiotropic effects. This study sought to compare the effects of losartan and telmisartan on pancreatic islets remodelling and glucose homeostasis in diet-induced obese mice. High-fat diet yielded overweight, insulin resistance, islet apoptosis and hypertrophy. Suitable insulin levels and preserved endocrine pancreas structure were correlated to adequate AKT-FOXO1 pathway functioning in losartan-treated animals...
October 22, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27779587/the-renin-inhibitor-aliskiren-protects-rat-lungs-from-the-histopathological-effects-of-fat-embolism
#18
Amanda N Fletcher, Agostino Molteni, Rakesh Ponnapureddy, Chirag Patel, Mark Pluym, Alan M Poisner
BACKGROUND: Fat embolism (FE) and the consequent fat embolism syndrome (FES) occurring after trauma or surgery can lead to serious pulmonary injury, including ARDS and death. Current treatment of FES is limited to supportive therapy. We have shown in a rat model that the renin angiotensin system (RAS) plays a significant role in the pathophysiology of FE since drugs interfering with the RAS, captopril and losartan, reduce the histopathologic pulmonary damage. The purpose of the current study was to determine if inhibition of renin by aliskiren, an FDA-approved drug for treating hypertension, would produce effective protection in the same model...
October 25, 2016: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/27779478/the-effect-of-the-angiotensin-ii-receptor-type-1-receptor-antagonists-losartan-and-telmisartan-on-thioacetamide-induced-liver-fibrosis-in-rats
#19
G Czechowska, K Celinski, A Korolczuk, G Wojcicka, J Dudka, A Bojarska, A Madro, T Brzozowski
It has been reported previously that the density of angiotensin II receptors is increased in the rat liver in experimentally-induced fibrosis. We hypothesized that pharmacological blockade of angiotensin receptors may produce beneficial effects in models of liver fibrosis. In this study, we used the widely used thioacetamide (TAA)-induced model of liver fibrosis (300 mg/L TAA ad libitum for 12 weeks). Rats received daily injections (i.p), lasting 4 weeks of the angiotensin II type 1 receptor antagonists, losartan 30 mg/kg (TAA + L) or telmisartan 10 mg/kg (TAA + T) and were compared to rat that received TAA alone...
August 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/27770539/inhibiting-microrna-503-and-microrna-181d-with-losartan-ameliorates-diabetic-nephropathy-in-kkay-mice
#20
XinWang Zhu, CongXiao Zhang, QiuLing Fan, XiaoDan Liu, Gang Yang, Yi Jiang, LiNing Wang
BACKGROUND Diabetic nephropathy (DN) is the most lethal diabetic microvascular complication; it is a major cause of renal failure, and an increasingly globally prominent healthcare problem. MATERIAL AND METHODS To identify susceptible microRNAs for the pathogenesis of DN and the targets of losartan treatment, microRNA arrays were employed to survey the glomerular microRNA expression profiles of KKAy mice treated with or without losartan. KKAy mice were assigned to either a losartan-treated group or a non-treatment group, with C57BL/6 mice used as a normal control...
October 22, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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