Doxazosin, a drug commonly prescribed for hypertension and prostate disease, increases heart failure risk. However, the underlying mechanism remains unclear. Galectin-3 is an important mediator that plays a pathogenic role in cardiac hypertrophy and heart failure. In the present study, we investigated whether doxazosin could stimulate galectin-3 expression and collagen synthesis in cultured HL-...

Background: Neutrophil recruitment to the airway is thought to be an important component of continuing inflammation and progression of chronic obstructive pulmonary disease (COPD), particularly in the presence of severe α1-antitrypsin (α1-AT) deficiency. However, the chemoattractant nature of secretions from these patients has yet to be clarified. Methods: The chemotactic activity of spontaneou...

Angiotensin II (ANG II) and norepinephrine (NE) are important regulators of vascular function and structure. Recent studies showed that there are multiple interactions between these two potent vasoconstrictor agents. The present experiment was designed to investigate the effect of NE on the expression of the type 1 ANG II receptor (AT1) in the aorta and cultured vascular smooth muscle cells (VS...

Recent studies on the pathogenic mechanisms of recessive hyperekplexia indicate disturbances in glycine receptor (GlyR) α1 biogenesis. Here, we examine the properties of a range of novel glycine receptor mutants identified in human hyperekplexia patients using expression in transfected cell lines and primary neurons. All of the novel mutants localized in the large extracellular domain of the Gl...

This positron emission tomography (PET) study aimed to further define selectivity of [(11)C]Ro15-4513 binding to the GABARα5 relative to the GABARα1 benzodiazepine receptor subtype. The impact of zolpidem, a GABARα1-selective agonist, on [(11)C]Ro15-4513, which shows selectivity for GABARα5, and the nonselective benzodiazepine ligand [(11)C]flumazenil binding was assessed in humans. Compartment...

In animals, the recovery of motoneuron excitability in the months following a complete spinal cord injury is mediated, in part, by increases in constitutive serotonin (5-HT2) and norepinephrine (α1) receptor activity, which facilitates the reactivation of calcium-mediated persistent inward currents (CaPICs) without the ligands serotonin and norepinephrine below the injury. In this study we soug...

45 46 In animals, the recovery of motoneuron excitability in the months following a complete spinal cord 47 injury is mediated, in part, by increases in constitutive serotonin (5HT2) and noradrenaline (α1) 48 receptor activity, which facilitates the reactivation of calcium-mediated persistent inward currents 49 (CaPICs) without the ligands serotonin and noradrenaline below the injury. Here, we ...

We have previously observed that intracoronary administration of the α1-adrenergic agonist phenylephrine (PE) over a period of minutes induced both an immediate and long-lasting (2 h) vasoconstriction of epicardial coronary arterioles. Because it is unlikely that α1-adrenergic constriction would persist for hours after removal of the agonist, this observation supports the view that another cons...

AIMS CD163 is a macrophage receptor for haemoglobin-haptoglobin (Hb-Hp) complexes, responsible for the clearance of haemoglobin. We hypothesized that production of soluble CD163 (sCD163) may be due to proleolytic shedding of membrane CD163 by neutrophil elastase, reported to be increased in culprit atherosclerotic plaques. We analysed the relationship between CD163 solubilization and elastase i...

Dysfunction of the right ventricle (RV) is closely related to prognosis for patients with RV failure. Therefore, strategies to improve failing RV function are significant. In a mouse RV failure model, we previously reported that α1-adrenergic receptor (α1-AR) inotropic responses are increased. The present study determined the roles of both predominant cardiac α1-AR subtypes (α1A and α1B) in upr...