keyword
https://read.qxmd.com/read/35048948/the-sympathetic-nervous-system-exacerbates-carotid-body-sensitivity-in-hypertension
#21
JOURNAL ARTICLE
Igor S A Felippe, Tymoteusz Zera, Melina P da Silva, Davi J A Moraes, Fiona McBryde, Julian F R Paton
AIMS: The carotid bodies (CB) of spontaneously hypertensive (SH) rats exhibit hypertonicity and hyperreflexia contributing to heightened peripheral sympathetic outflow. We hypothesized that CB hyperexcitability is driven by its own sympathetic innervation. METHODS AND RESULTS: To test this, the chemoreflex was activated (NaCN 50-100 µL, 0.04%) in SH and Wistar rats in situ before and after: 1) electrical stimulation (ES; 30 Hz, 2 ms, 10 V) of the superior cervical ganglion (SCG), which innervates the CB; 2) unilateral resection of the SCG (SCGx); 3) CB injections of an α1-adrenergic receptor agonist (phenylephrine, 50 µL, 1 mmol/L), and 4) α1-adrenergic receptor antagonist prazosin (30 µL, 1 mmol/L) or tamsulosin (50 µL, 1 mmol/l)...
January 20, 2022: Cardiovascular Research
https://read.qxmd.com/read/34984343/region-specific-effects-of-antenatal-early-postnatal-hypothyroidism-on-endothelial-no-pathway-activity-in-systemic-circulation
#22
JOURNAL ARTICLE
Dina K Gaynullina, Svetlana I Sofronova, Ekaterina K Selivanova, Anastasia A Shvetsova, Anna A Borzykh, Olga S Tarasova
BACKGROUND: Antenatal/early postnatal hypothyroidism weakens NO-mediated anticontractile influence of endothelium in coronary arteries of adult rats, but it remains unclear whether this occurs in other vascular regions. We hypothesized that developmental thyroid deficiency is followed by region-specific changes in the endothelial NO-pathway activity in systemic vasculature. To explore this, we estimated the effects of antenatal/early postnatal hypothyroidism on NO-pathway activity and its potential local control mechanisms in rat mesenteric and skeletal muscle (sural) arteries...
2022: Current research in physiology
https://read.qxmd.com/read/34973951/crosstalk-relationship-between-adiponectin-receptors-ppar-%C3%AE-and-%C3%AE-adrenoceptors-in-renal-vasculature-of-diabetic-wkys
#23
JOURNAL ARTICLE
Sheryar Afzal, Munavvar Abdul Sattar, Olorunfemi A Eseyin, Ali Attiq, Edward James Johns
Hypoadiponectinemia is associated with renal dysfunctions. Irbesartan and pioglitazone activate Peroxisome proliferator-activated gamma receptor (PPAR-γ) as partial and full agonists. We investigated a crosstalk interaction and synergistic action between adiponectin receptors, PPAR-γ agonists in attenuating renal hemodynamics to adrenergic agonists in diabetic Wistar Kyoto rats (WKY). Streptozotocin (40 mg/kg) was used to induce diabetes, whereas, pioglitazone (10 mg/kg/day), irbesartan (30 mg/kg/day) administered orally for 28 days and adiponectin intraperitoneally (2...
December 30, 2021: European Journal of Pharmacology
https://read.qxmd.com/read/34882841/dexmedetomidine-protects-cardiomyocytes-against-hypoxia-reoxygenation-injury-via-multiple-mechanisms
#24
JOURNAL ARTICLE
Shunv Cai, Yixing Liu, Yun Cheng, Junbo Yuan, Jun Fang
BACKGROUND: Myocardial infarction (MI) is a serious cardiovascular disease associated with myocardial ischemia/reperfusion (I/R) injury. Dexmedetomidine (Dex), an α2-adrenoceptor agonist, has been reported to protect against I/R injury. We examined the cardioprotective effects of Dex on cardiomyocytes under hypoxia/reoxygenation (H/R) conditions and explored the underlying mechanisms. MATERIALS AND METHODS: A H/R model was established to mimic the MI injury. The CCK-8 assay was performed to measure cell viability...
July 2022: Journal of Clinical Laboratory Analysis
https://read.qxmd.com/read/34506777/dexmedetomidine-protects-the-heart-against-ischemia-reperfusion-injury-via-regulation-of-the-bradykinin-receptors
#25
JOURNAL ARTICLE
Jinchao Song, Jiankui Du, Xing Tan, Zhaotang Wu, Jihong Yuan, Binhai Cong
BACKGROUND: Dexmedetomidine (DEX) has been reported to protect the heart against ischemia reperfusion (I/R) injury. However, the exact mechanisms are still not fully understood. METHODS AND RESULTS: A rat cardiac I/R injury model was induced by ligation of the left anterior descending coronary artery for 1 h and subsequent reperfusion for 2 h, and DEX was administered intravenously 30 min before ischemia. We confirmed that DEX treatment mitigated cardiac I/R injury...
November 15, 2021: European Journal of Pharmacology
https://read.qxmd.com/read/34491515/the-anticonvulsant-effects-of-alpha-2-adrenoceptor-agonist-dexmedetomidine-on-pentylenetetrazole-induced-seizures-in-rats
#26
JOURNAL ARTICLE
Arzuhan Cetindag Ciltas, Ercan Ozdemir, Erkan Gumus, Ahmet Sevki Taskiran, Handan Gunes, Gokhan Arslan
Alpha2-adrenoreceptor (α2 -AR) is a noradrenergic receptor that is frequently studied for modulation of seizure activity. However, the precise role of this receptor agonists in regulating seizure activity is still unclear. Our aim in this study was to investigate the effects of α2 -AR agonist dexmedetomidine (DEX) and atipamezole (α2 -AR antagonist, ATI) on seziures in rats. In the study, 32 adult male Wistar Albino rats (weighing 220-260 g) were used. To induce seizures in rats, pentylenetetrazole (PTZ, 35 mg/kg) was injected intraperitoneally (i...
February 2022: Neurochemical Research
https://read.qxmd.com/read/34246652/the-rho-kinase-rock-inhibitor-y-27632-reduces-the-%C3%AE-2-adrenoceptor-density-but-enhance-camp-formation-in-primary-equine-bronchial-epithelial-cells
#27
JOURNAL ARTICLE
Linda Marie Schellenberg, Ralf Regenthal, Getu Abraham
The present study addresses the effect of the Rho-kinase (ROCK) inhibitor Y-27632 on the β2 -adrenoceptor density and β-agonist-stimulated intracellular second messenger cAMP formation in primary equine bronchial epithelial cells (EBEC). Y-27632 significantly decreased the β2 -adrenoceptor number (Bmax ) without markedly affecting the receptor affinity (dissociation constant, KD ) to the radioligand [125 I]-iodocyanopindolol (ICYP). In contrast, Y-27632 augmented the β-agonist-stimulated intracellular cAMP production...
September 15, 2021: European Journal of Pharmacology
https://read.qxmd.com/read/34001271/the-effects-of-clonidine-and-yohimbine-in-the-tail-flick-and-hot-plate-tests-in-the-naked-mole-rat-heterocephalus-glaber
#28
JOURNAL ARTICLE
R M Mwobobia, T I Kanui, K S P Abelson
OBJECTIVE: The naked mole rat (NMR) (Heterocephalus glaber) is increasingly considered an important biomedical research model for various conditions like hypoxic brain injury, cancer and nociception. This study was designed to investigate the effects of clonidine and yohimbine, an alpha-2 (α2 ) adrenoceptor agonist and antagonist respectively in the tail flick and hot plate tests. RESULTS: A significant difference in tail flick latency was noted between saline control and 30 µg/kg clonidine, which was reduced after administration of 30 µg/kg yohimbine...
May 17, 2021: BMC Research Notes
https://read.qxmd.com/read/33950785/evaluation-of-analgesic-interaction-between-morphine-maropitant-and-dexmedetomidine-in-dogs-undergoing-ovariohysterectomy
#29
JOURNAL ARTICLE
S R Karna, P Chambers, P Singh, N Lopez-Villalobos, K Kongara
AIMS: To compare the analgesic effect of morphine combined with maropitant and/or dexmedetomidine to morphine alone but at a higher dose, and to evaluate the pharmacokinetics of the drug combinations, in dogs undergoing ovariohysterectomy (OHE). METHODS: Forty client-owned dogs were randomised into four treatment groups (n = 10 per group) each to receive a different analgesic protocol. After premedication with I/M acepromazine, anaesthesia was induced with propofol to effect and maintained with isoflurane in 100% oxygen delivered via a circle system...
January 2022: New Zealand Veterinary Journal
https://read.qxmd.com/read/33923625/role-of-%C3%AE-2-adrenoceptor-subtypes-in-suppression-of-l-type-ca-2-current-in-mouse-cardiac-myocytes
#30
JOURNAL ARTICLE
Edward V Evdokimovskii, Ryounghoon Jeon, Sungjo Park, Oleg Y Pimenov, Alexey E Alekseev
Sarcolemmal α2 adrenoceptors (α2-AR), represented by α2A, α2B and α2C isoforms, can safeguard cardiac muscle under sympathoadrenergic surge by governing Ca2+ handling and contractility of cardiomyocytes. Cardiomyocyte-specific targeting of α2-AR would provide cardiac muscle-delimited stress control and enhance the efficacy of cardiac malfunction treatments. However, little is known about the specific contribution of the α2-AR subtypes in modulating cardiomyocyte functions. Herein, we analyzed the expression profile of α2A, α2B and α2C subtypes in mouse ventricle and conducted electrophysiological antagonist assay evaluating the contribution of these isoforms to the suppression of L-type Ca2+ current ( I CaL )...
April 16, 2021: International Journal of Molecular Sciences
https://read.qxmd.com/read/33677066/regulation-of-basal-and-norepinephrine-induced-camp-and-i-ca-in-hipsc-cardiomyocytes-effects-of-culture-conditions-and-comparison-to-adult-human-atrial-cardiomyocytes
#31
JOURNAL ARTICLE
Zafar Iqbal, Djemail Ismaili, Bernardo Dolce, Johannes Petersen, Hermann Reichenspurner, Arne Hansen, Paulus Kirchhof, Thomas Eschenhagen, Viacheslav O Nikolaev, Cristina E Molina, Torsten Christ
BACKGROUND: There is ongoing interest in generating cardiomyocytes derived from human induced pluripotent stem cells (hiPSC) to study human cardiac physiology and pathophysiology. Recently we found that norepinephrine-stimulated calcium currents (ICa ) in hiPSC-cardiomyocytes were smaller in conventional monolayers (ML) than in engineered heart tissue (EHT). In order to elucidate culture specific regulation of β1 -adrenoceptor (β1 -AR) responses we investigated whether action of phosphodiesterases (PDEs) may limit norepinephrine effects on ICa and on cytosolic cAMP in hiPSC-cardiomyocytes...
June 2021: Cellular Signalling
https://read.qxmd.com/read/33626966/nahs-subchronic-treatment-improves-hypertension-induced-by-traumatic-brain-injury-in-rats-through-vasopressor-sympathetic-outflow-inhibition
#32
JOURNAL ARTICLE
Saul Huerta de la Cruz, Luisa Rocha, Cindy Santiago-Castañeda, Araceli Sanchez-Lopez, Alma D Pinedo-Rodriguez, Grecia J Medina-Terol, David Centurion
Traumatic Brain Injury (TBI) represents a critical public health problem around the world. Up to date, there are no accurate therapeutic approaches for the treatment of cardiovascular impairments induce by TBI. In this regard, hydrogen sulfide, a novel gasotransmitter, has been proposed as a neuro- and cardio-protective molecule. This study was designed to determine the effect of subchronic treatment with NaHS on hemodynamic, vasopressor sympathetic outflow and sensorimotor alterations produced by TBI. Animals were submitted to lateral fluid percussion injury model and changes in hemodynamic variables were measured by pletismographic methods...
February 25, 2021: Journal of Neurotrauma
https://read.qxmd.com/read/33604602/alpha-1-adrenoceptor-signalling-contributes-to-toxic-effects-of-catecholamine-on-electrical-properties-in-cardiomyocytes
#33
JOURNAL ARTICLE
Mengying Huang, Xuehui Fan, Zhen Yang, Lukas Cyganek, Xin Li, Goekhan Yuecel, Huan Lan, Yingrui Li, Angela Wendel, Siegfried Lang, Karen Bieback, Ibrahim El-Battrawy, Xiaobo Zhou, Ibrahim Akin, Martin Borggrefe
AIMS: This study aimed to investigate possible roles and underlying mechanisms of alpha-adrenoceptor coupled signalling for the pathogenesis of Takotsubo syndrome (TTS). METHODS AND RESULTS: Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were treated with a toxic concentration of epinephrine (Epi, 0.5 mM for 1 h) to mimic the setting of TTS. Patch-clamp technique, polymerase chain reaction (PCR) and Fluorescence-activated cell sorting (FACS) were employed for the study...
July 18, 2021: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://read.qxmd.com/read/33339892/central-dopamine-d-2-receptors-regulate-plasma-glucose-levels-in-mice-through-autonomic-nerves
#34
JOURNAL ARTICLE
Hiroko Ikeda, Naomi Yonemochi, Risa Mikami, Manabu Abe, Meiko Kawamura, Rie Natsume, Kenji Sakimura, John L Waddington, Junzo Kamei
Recent evidence suggests that the central nervous system (CNS) regulates plasma glucose levels, but the underlying mechanism is unclear. The present study investigated the role of dopaminergic function in the CNS in regulation of plasma glucose levels in mice. I.c.v. injection of neither the dopamine D1 receptor agonist SKF 38393 nor the antagonist SCH 23390 influenced plasma glucose levels. In contrast, i.c.v. injection of both the dopamine D2 receptor agonist quinpirole and the antagonist l-sulpiride increased plasma glucose levels...
December 18, 2020: Scientific Reports
https://read.qxmd.com/read/33132694/paradoxical-bronchoconstriction-caused-by-%C3%AE-2-adrenoceptor-agonists
#35
JOURNAL ARTICLE
Khadija Ayed, Islam Latifa Hadj Khalifa, Salma Mokaddem, Saloua Ben Khamsa Jameleddine
INTRODUCTION: Salbutamol and terbutaline are short-acting β2 adrenergic agonists that produce bronchial smooth muscle relaxation and are widely used in obstructive pulmonary diseases. Nevertheless, their use has been the cause of a paradoxical bronchoconstriction, which is a rare and potentially serious adverse reaction. The aim of this study is to report a case of paradoxical bronchoconstriction caused by β2 adrenergic agonists. METHODS: This case is about a 50-year-old asthmatic patient who describes a history of repeated acute asthma attacks after salbutamol inhalation or terbutaline nebulization...
2020: Drug Target Insights
https://read.qxmd.com/read/33131340/efficacy-and-safety-of-triple-combination-therapy-for-treating-chronic-obstructive-pulmonary-disease-an-expert-review
#36
REVIEW
Beatrice Ludovica Ritondo, Ermanno Puxeddu, Luigino Calzetta, Mario Cazzola, Paola Rogliani
Introduction : The current recommendations of chronic obstructive pulmonary disease (COPD) suggest to escalate from inhaled corticosteroid/long-acting β2 -adrenoceptor agonist (ICS/LABA) treatment to triple therapy in patients experiencing persistent breathlessness, exercise limitation, or exacerbation. The addition of an ICS to LABA/long-acting muscarinic antagonist (LAMA) combination is recommended for frequently exacerbating patients with high levels of blood eosinophils. Nowadays, three triple therapies have been approved as fixed-dose combinations (FDCs) for the treatment of COPD: beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FOR/GLY), fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI), and budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR)...
April 2021: Expert Opinion on Pharmacotherapy
https://read.qxmd.com/read/32932742/agonist-binding-and-g-protein-coupling-in-histamine-h-2-receptor-a-molecular-dynamics-study
#37
JOURNAL ARTICLE
Marcus Conrad, Christian A Söldner, Yinglong Miao, Heinrich Sticht
The histamine H2 receptor (H2 R) plays an important role in the regulation of gastric acid secretion. Therefore, it is a main drug target for the treatment of gastroesophageal reflux or peptic ulcer disease. However, there is as of yet no 3D-structural information available hampering a mechanistic understanding of H2 R. Therefore, we created a model of the histamine-H2 R-Gs complex based on the structure of the ternary complex of the β2-adrenoceptor and investigated the conformational stability of this active GPCR conformation...
September 12, 2020: International Journal of Molecular Sciences
https://read.qxmd.com/read/32907576/navafenterol-azd8871-in-patients-with-mild-asthma-a-randomised-placebo-controlled-phase-i-study-evaluating-the-safety-tolerability-pharmacokinetics-and-pharmacodynamics-of-single-ascending-doses-of-this-novel-inhaled-long-acting-dual-pharmacology-bronchodilator
#38
JOURNAL ARTICLE
Eulalia Jimenez, Carol Astbury, Muna Albayaty, Ulrika Wählby-Hamrén, Beatriz Seoane, Cristina Villarroel, Helena Pujol, Maria Jesus Bermejo, Ajay Aggarwal, Ioannis Psallidas
BACKGROUND: Navafenterol (AZD8871) is an inhaled long-acting dual-pharmacology muscarinic antagonist/β2 -adrenoceptor agonist (MABA) in development for the treatment of obstructive airways diseases. The safety, tolerability, pharmacodynamics, and pharmacokinetics of navafenterol were investigated in patients with mild asthma. METHODS: This was a randomised, single-blind, placebo-controlled, single-ascending-dose study. Patients were randomly assigned to one of two cohorts which evaluated escalating doses of navafenterol (50-2100 μg) in an alternating manner over three treatment periods...
September 9, 2020: Respiratory Research
https://read.qxmd.com/read/32907575/navafenterol-azd8871-in-healthy-volunteers-safety-tolerability-and-pharmacokinetics-of-multiple-ascending-doses-of-this-novel-inhaled-long-acting-dual-pharmacology-bronchodilator-in-two-phase-i-randomised-single-blind-placebo-controlled-studies
#39
JOURNAL ARTICLE
Victor Balaguer, Muna Albayaty, Eulalia Jimenez, Ulrika Wählby-Hamrén, Carol Astbury, Beatriz Seoane, Marie-Pierre Malice, Alejhandra Lei, Ajay Aggarwal, Ioannis Psallidas
BACKGROUND: Navafenterol (AZD8871) is a novel, long-acting, dual-pharmacology (muscarinic receptor antagonist and β2- adrenoceptor agonist) molecule in development for chronic obstructive pulmonary disease and asthma. METHODS: These two phase I, randomised, single-blind, multiple-ascending-dose studies evaluated inhaled navafenterol and placebo (3:1 ratio) in healthy, male, non-Japanese (study A; NCT02814656) and Japanese (study B; NCT03159442) volunteers. In each study, volunteers were dosed in three cohorts, allowing gradual dose escalation from 300 μg to 600 μg to 900 μg...
September 9, 2020: Respiratory Research
https://read.qxmd.com/read/32882146/new-drugs-under-development-for-copd
#40
REVIEW
Federica Lo Bello, Philip M Hansbro, Chantal Donovan, Irene Coppolino, Sharon Mumby, Ian M Adcock, Gaetano Caramori
INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by chronic bronchitis, emphysema, and remodeling. Its prevalence is increasing worldwide; however, there are few effective therapies, and none of the treatments currently available prevent the progression of the disease or target all of the hallmark features. The development and progression of COPD are heterogeneous, which has hampered the development of new therapies. AREAS COVERED: In this review, we cover the emergence of the improvement of existing classes of drugs including glucocorticoids, β2-adrenoceptor agonists, phosphodiesterase inhibitors, PDE4 selective inhibitors, PDE3/PDE4 inhibitors, protease inhibitors, recombinant α1-antitrypsin and neutrophil elastase inhibitors...
December 2020: Expert Opinion on Emerging Drugs
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