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α1 receptor blockade

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https://www.readbyqxmd.com/read/28492488/redistribution-of-cerebral-blood-flow-during-severe-hypovolemia-and-reperfusion-in-a-sheep-model-critical-role-of-%C3%AE-1-adrenergic-signaling
#1
René Schiffner, Sabine Juliane Bischoff, Thomas Lehmann, Florian Rakers, Sven Rupprecht, Juliane Reiche, Georg Matziolis, Harald Schubert, Matthias Schwab, Otmar Huber, Martin Schmidt
BACKGROUND: Maintenance of brain circulation during shock is sufficient to prevent subcortical injury but the cerebral cortex is not spared. This suggests area-specific regulation of cerebral blood flow (CBF) during hemorrhage. METHODS: Cortical and subcortical CBF were continuously measured during blood loss (≤50%) and subsequent reperfusion using laser Doppler flowmetry. Blood gases, mean arterial blood pressure (MABP), heart rate and renal blood flow were also monitored...
May 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28455782/rpc4046-a-novel-anti-interleukin-13-antibody-blocks-il-13-binding-to-il-13-%C3%AE-1-and-%C3%AE-2-receptors-a-randomized-double-blind-placebo-controlled-dose-escalation-first-in-human-study
#2
Catherine S Tripp, Carolyn Cuff, Andrew L Campbell, Barbara A Hendrickson, Jeff Voss, Terry Melim, Chengbin Wu, Andrew D Cherniack, Kenneth Kim
INTRODUCTION: A unique anti-interleukin (IL)-13 monoclonal antibody, RPC4046, was generated on the basis of differential IL-13 receptor (R) blockade as assessed in a murine asthma model; the safety, tolerability, pharmacokinetics, and pharmacodynamics of RPC4046 were evaluated in a first-in-human study. METHODS: Anti-IL-13 antibodies with varying receptor blocking specificity were evaluated in the ovalbumin-induced murine asthma model. A randomized, double-blind, placebo-controlled, dose-escalation first-in-human study (NCT00986037) was conducted with RPC4046 in healthy adults and patients with mild to moderate controlled asthma...
April 28, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28392265/norepinephrine-regulates-cocaine-primed-reinstatement-via-%C3%AE-1-adrenergic-receptors-in-the-medial-prefrontal-cortex
#3
Karl T Schmidt, Jason P Schroeder, Stephanie L Foster, Katherine Squires, Brilee M Smith, Elizabeth G Pitts, Michael P Epstein, David Weinshenker
Drug-primed reinstatement of cocaine seeking in rats is thought to reflect relapse-like behavior and is mediated by the integration of signals from mesocorticolimbic dopaminergic projections and corticostriatal glutamatergic innervation. Cocaine-primed reinstatement can also be attenuated by systemic administration of dopamine β-hydroxylase (DBH) inhibitors, which prevent norepinephrine (NE) synthesis, or by α1-adrenergic receptor (α1AR) antagonists, indicating functional modulation by the noradrenergic system...
April 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28390894/methylene-blue-inhibits-gabaa-receptors-by-interaction-with-gaba-binding-site
#4
Zhenglan Chen, Ran Liu, Shao-Hua Yang, Glenn H Dillon, Renqi Huang
Methylene blue (MB) is commonly used in diagnostic procedures and is also used to treat various medical conditions. Neurological effects of MB have been reported in clinical observations and experimental studies. Thus the modulation of GABAA receptor function by MB was investigated. Whole-cell GABA-activated currents were recorded from HEK293 cells expressing various GABAA receptor subunit configurations. MB inhibition of GABA currents was apparent at 3 μM, and it had an IC50 of 31 μM in human α1β2γ2 receptors...
April 5, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28298638/pnaktide-attenuates-steatohepatitis-and-atherosclerosis-by-blocking-na-k-atpase-ros-amplification-in-c57bl6-and-apoe-knockout-mice-fed-a-western-diet
#5
Komal Sodhi, Krithika Srikanthan, Perrine Goguet-Rubio, Alexandra Nichols, Amrita Mallick, Athar Nawab, Rebecca Martin, Preeya T Shah, Muhammad Chaudhry, Saroj Sigdel, Mehiar El-Hamdani, Jiang Liu, Zijian Xie, Nader G Abraham, Joseph I Shapiro
We have previously reported that the α1 subunit of sodium potassium adenosine triphosphatase (Na/K-ATPase), acts as a receptor and an amplifier for reactive oxygen species, in addition to its distinct pumping function. On this background, we speculated that blockade of Na/K-ATPase-induced ROS amplification with a specific peptide, pNaKtide, might attenuate the development of steatohepatitis. To test this hypothesis, pNaKtide was administered to a murine model of NASH: the C57Bl6 mouse fed a "western" diet containing high amounts of fat and fructose...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28294424/therapeutic-regulation-of-systemic-inflammation-in-xenograft-recipients
#6
Hayato Iwase, Hong Liu, Tao Li, Zhongquiang Zhang, Bingsi Gao, Hidetaka Hara, Martin Wijkstrom, Cassandra Long, Ryan Saari, David Ayares, David K C Cooper, Mohamed B Ezzelarab
Inflammation is known to preclude tolerance after transplantation. We have previously shown that systemic inflammation in xenograft recipients (SIXR) precedes activation of coagulation in the absence of T cell responses. Accordingly, SIXR may amplify innate and adaptive immune responses against xenografts after pig-to-primate xenotransplantation, even with efficient immunosuppressive therapy. We evaluated the impact of anti-inflammatory agents on pro-inflammatory cytokines and chemokines in pig artery patch and heart xenograft recipients...
March 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28212941/injections-of-the-of-the-%C3%AE-1-adrenoceptor-antagonist-prazosin-into-the-median-raphe-nucleus-increase-food-intake-and-fos-expression-in-orexin-neurons-of-free-feeding-rats
#7
Eduardo Simão da Silva, Rafael Appel Flores, Anderson Savaris Ribas, Ana Paula Taschetto, Moacir Serralvo Faria, Leandro Bueno Lima, Martin Metzger, José Donato, Marta Aparecida Paschoalini
Previously, we showed that the blockade of α1-adrenoreceptors in the median raphe nucleus (MnR) increased food intake in free-feeding rats, indicating that adrenergic mechanisms in the MnR participate in the regulation of food intake. However, the impact of such a pharmacological manipulation on other neural circuits related to food intake remains unknown. In the current study, we sought to identify forebrain regions which are responsive to α1-adrenergic receptor blockade and presumably involved in the modulation of the feeding response...
May 1, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28199786/alpha-adrenergic-receptor-blockade-increases-capillarisation-and-fractional-o2-extraction-and-lowers-blood-flow-in-contracting-human-skeletal-muscle
#8
Stefan P Mortensen, Stuart Egginton, Mads Madsen, Jonas B Hansen, Gregers D W Munch, Ulrik Winning Iepsen, Thorbjörn Åkerström, Bente K Pedersen, Ylva Hellsten
AIM: To investigate the effect of elevated basal shear stress on angiogenesis in humans, and the role of enhanced skeletal muscle capillarisation on blood flow and O2 extraction. METHODS: Limb haemodynamics and O2 extraction was measured at rest and during one-leg knee-extensor exercise (12 and 24W) in 10 healthy untrained young men before and after 4 weeks treatment with an α1 receptor-antagonist (Terazosin, 1-2 mg day(-1) ). Corresponding biopsies were taken from the m...
February 15, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28029729/combined-treatment-with-dipeptidyl-peptidase-4-inhibitor-sitagliptin-and-angiotensin-ii-type-1-receptor-blocker-losartan-suppresses-progression-in-a-non-diabetic-rat-model-of-steatohepatitis
#9
Yasushi Okura, Tadashi Namisaki, Kei Moriya, Mitsuteru Kitade, Kosuke Takeda, Kosuke Kaji, Ryuichi Noguchi, Norihisa Nishimura, Kenichiro Seki, Hideto Kawaratani, Hiroaki Takaya, Shinya Sato, Yasuhiko Sawada, Naotaka Shimozato, Masanori Furukawa, Keisuke Nakanishi, Soichiro Saikawa, Takuya Kubo, Kiyoshi Asada, Hitoshi Yoshiji
AIM: Dipeptidyl peptidase-4 (DPP4) inhibitors (DPP4-I) are oral glucose-lowering drugs for type 2 diabetes mellitus. Previously, we reported that DPP4-I (sitagliptin) exerted suppressive effects on experimental liver fibrosis in rats. Blockade of the renin-angiotensin system by angiotensin-II type 1 receptor blocker (losartan), commonly used in the management of hypertension, has been shown to significantly alleviate hepatic fibrogenesis and carcinogenesis. We aimed to elucidate the effects and possible mechanisms of a sitagliptin + losartan combination on the progression of non-diabetic non-alcoholic steatohepatitis (NASH) in a rat model...
December 28, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/27812496/reversible-exacerbation-of-obstructive-sleep-apnea-by-%C3%AE-1-adrenergic-blockade-with-tamsulosin-a-case-report
#10
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/27769919/preoperative-levels-of-catecholamines-and-metanephrines-and-intraoperative-hemodynamics-of-patients-undergoing-pheochromocytoma-and-paraganglioma-resection
#11
Toby N Weingarten, Tasha L Welch, Tamara L Moore, Gulshat F Walters, Joni L Whipple, Alexandre Cavalcante, Irina Bancos, William F Young, Lucinda M Gruber, Muhammad Z Shah, Travis J McKenzie, Darrell R Schroeder, Juraj Sprung
OBJECTIVE: To determine whether, despite pharmacologic adrenergic receptor blockade, higher preoperative levels of catecholamines and metanephrines (adrenergic activity) are associated with increased intraoperative complications. MATERIALS AND METHODS: Records of patients undergoing paraganglioma and pheochromocytoma (PGL-PCC) resection from January 1, 2000, to June 30, 2015, were reviewed for preoperative levels of adrenergic activity, intraoperative variability in blood pressure and heart rate (range), and postoperative outcomes (hypotension requiring treatment)...
October 18, 2016: Urology
https://www.readbyqxmd.com/read/27754015/br-04-1management-of-treatment-resistant-hypertension
#12
David John Webb
Treatment-resistant hypertension (TRH) is defined as the failure to achieve an office BP target of <140/90 mmHg (<130/80 mmHg in patients with chronic kidney disease (CKD) or diabetes) in patients with hypertension (HT), despite adherence to at least 3 antihypertensive medications at optimal tolerated doses, ideally including a diuretic (Calhoun et al., Circulation 2008). TRH identifies patients with hard-to-treat HT, who might benefit from specialist investigation and treatment. Although some studies put the prevalence of TRH as >10%, these levels may be inflated by white-coat hypertension and poor adherence...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27702852/antiadrenergic-autoimmunity-in-postural-tachycardia-syndrome
#13
Artur Fedorowski, Hongliang Li, Xichun Yu, Kristi A Koelsch, Valerie M Harris, Campbell Liles, Taylor A Murphy, Syed M S Quadri, Robert Hal Scofield, Richard Sutton, Olle Melander, David C Kem
AIMS: Postural tachycardia syndrome (POTS), a common and debilitating cardiovascular disorder, is characterized by an exaggerated heart rate increase during orthostasis and a wide spectrum of adrenergic-related symptoms. To determine the aetiology of POTS, we examined a possible pathophysiological role for autoantibodies against α1-adrenergic (α1AR) and β1/2-adrenergic receptors (β1/2AR). METHODS AND RESULTS: Immunoglobulin G (IgG) derived from 17 POTS patients, 7 with recurrent vasovagal syncope (VVS), and 11 normal controls was analysed for its ability to modulate activity and ligand responsiveness of α1AR and β1/2AR in transfected cells and to alter contractility of isolated rat cremaster arterioles in vitro...
October 4, 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/27228963/dynamic-cerebral-autoregulation-is-unrelated-to-decrease-in-external-carotid-artery-blood-flow-during-acute-hypotension-in-healthy-young-men
#14
Shigehiko Ogoh, Henrik Sørensen, Ai Hirasawa, Hiroyuki Sasaki, Takuro Washio, Takeshi Hashimoto, Damian M Bailey, Niels H Secher
What is the central question of this study? Dynamic cerebral autoregulation (CA) is impaired by sympathetic blockade, and the external carotid artery (ECA) vascular bed may prevent adequate internal carotid artery blood flow. We examined whether α1 -receptor blockade-induced attenuation of dynamic CA is related to reduced ECA vasoconstriction. What is the main finding and its importance? α1 -Receptor blockade attenuated dynamic CA, but in contrast to our hypothesis did not affect the ECA blood flow response to acute hypotension...
August 1, 2016: Experimental Physiology
https://www.readbyqxmd.com/read/27211864/integrin-%C3%AE-1%C3%AE-1-protects-against-signs-of-post-traumatic-osteoarthritis-in-the-female-murine-knee-partially-via-regulation-of-epidermal-growth-factor-receptor-signalling
#15
S Y Shin, A Pozzi, S K Boyd, A L Clark
OBJECTIVE: To investigate the role of integrin α1β1 in the progression of post-traumatic osteoarthritis (PTOA), and elucidate the contribution of epidermal growth factor receptor (EGFR) signalling to the mechanism by which integrin α1β1 might control PTOA. We hypothesised that integrin α1β1 plays a protective role in the course of PTOA and that the effect of PTOA (e.g., synovitis, loss of cartilage and growth of osteophytes) would be exacerbated in mice lacking integrin α1β1 at every time point post destabilisation of medial meniscus (DMM)...
October 2016: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/27138566/the-anti-hypertensive-drug-prazosin-inhibits-glioblastoma-growth-via-the-pkc%C3%AE-dependent-inhibition-of-the-akt-pathway
#16
Suzana Assad Kahn, Silvia Lima Costa, Sharareh Gholamin, Ryan T Nitta, Luiz Gustavo Dubois, Marie Fève, Maria Zeniou, Paulo Lucas Cerqueira Coelho, Elias El-Habr, Josette Cadusseau, Pascale Varlet, Siddhartha S Mitra, Bertrand Devaux, Marie-Claude Kilhoffer, Samuel H Cheshier, Vivaldo Moura-Neto, Jacques Haiech, Marie-Pierre Junier, Hervé Chneiweiss
A variety of drugs targeting monoamine receptors are routinely used in human pharmacology. We assessed the effect of these drugs on the viability of tumor-initiating cells isolated from patients with glioblastoma. Among the drugs targeting monoamine receptors, we identified prazosin, an α1- and α2B-adrenergic receptor antagonist, as the most potent inducer of patient-derived glioblastoma-initiating cell death. Prazosin triggered apoptosis of glioblastoma-initiating cells and of their differentiated progeny, inhibited glioblastoma growth in orthotopic xenografts of patient-derived glioblastoma-initiating cells, and increased survival of glioblastoma-bearing mice...
2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27118715/the-norepinephrine-reuptake-inhibitor-reboxetine-is-more-potent-in-treating-murine-narcoleptic-episodes-than-the-serotonin-reuptake-inhibitor-escitalopram
#17
Christian Schmidt, Judith Leibiger, Markus Fendt
One of the major symptoms of narcolepsy is cataplexy, a sudden loss of muscle tone. Despite the advances in understanding the neuropathology of narcolepsy, cataplexy is still treated symptomatically with antidepressants. Here, we investigate in a murine narcolepsy model the hypothesis that the antidepressants specifically blocking norepinephrine reuptake are more potent in treating narcoleptic episodes than the antidepressants blocking of serotonin reuptake. Furthermore, we tested the effects of α1 receptor stimulation and blockade, respectively, on narcoleptic episodes...
July 15, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27091617/-lumbar-sympathectomy-literature-review-over-the-past-15-years
#18
REVIEW
M Pekař, M Mazur, A Pekařová, J Kozák, A Foltys
INTRODUCTION: Lumbar sympathectomy (LS) irreversibly damages a part of the sympathetic trunk and adjacent ganglia between L1 and L5, typically between L2 and L4. The first LS was performed in 1923. Initially, it used to be performed very often; however, with the progress of vascular and endovascular surgery its importance gradually continues to decline. The aim of the paper is to present literature review focusing on LS over the past 15 years. METHOD: Literature review of 113 academic articles found in academic journal databases...
March 2016: Rozhledy V Chirurgii: Měsíčník Československé Chirurgické Společnosti
https://www.readbyqxmd.com/read/27016578/selective-%C3%AE-1-adrenergic-blockade-disturbs-the-regional-distribution-of-cerebral-blood-flow-during-static-handgrip-exercise
#19
Igor A Fernandes, João D Mattos, Monique O Campos, Alessandro C Machado, Marcos P Rocha, Natalia G Rocha, Lauro C Vianna, Antonio C L Nobrega
Handgrip-induced increases in blood flow through the contralateral artery that supplies the cortical representation of the arm have been hypothesized as a consequence of neurovascular coupling and a resultant metabolic attenuation of sympathetic cerebral vasoconstriction. In contrast, sympathetic restraint, in theory, inhibits changes in perfusion of the cerebral ipsilateral blood vessels. To confirm whether sympathetic nerve activity modulates cerebral blood flow distribution during static handgrip (SHG) exercise, beat-to-beat contra- and ipsilateral internal carotid artery blood flow (ICA; Doppler) and mean arterial pressure (MAP; Finometer) were simultaneously assessed in nine healthy men (27 ± 5 yr), both at rest and during a 2-min SHG bout (30% maximal voluntary contraction), under two experimental conditions: 1) control and 2) α1-adrenergic receptor blockade...
June 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/26968030/the-combination-of-marketed-antagonists-of-%C3%AE-1b-adrenergic-and-5-ht2a-receptors-inhibits-behavioral-sensitization-and-preference-to-alcohol-in-mice-a-promising-approach-for-the-treatment-of-alcohol-dependence
#20
Fabrice Trovero, Sabrina David, Philippe Bernard, Alain Puech, Jean-Charles Bizot, Jean-Pol Tassin
Alcohol-dependence is a chronic disease with a dramatic and expensive social impact. Previous studies have indicated that the blockade of two monoaminergic receptors, α1b-adrenergic and 5-HT2A, could inhibit the development of behavioral sensitization to drugs of abuse, a hallmark of drug-seeking and drug-taking behaviors in rodents. Here, in order to develop a potential therapeutic treatment of alcohol dependence in humans, we have blocked these two monoaminergic receptors by a combination of antagonists already approved by Health Agencies...
2016: PloS One
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