ABSTRACT Heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of heart cases globally, and this incidence is increasing due to extended lifespans accumulating comorbidities. Emerging evidence suggests that Wnt signaling plays a role in cardiomyocyte hypertrophy cardiac fibrosis, which are key features HFpEF. Furthermore, Porcupine (PORCN) inhibitors, negatively regulate signaling, have shown promising results improving function reducing and/or fibrosis. This...

ABSTRACT Emerging evidence indicates that G‐protein coupled receptor 55 (GPR55), a nonclassic of the endocannabinoid system is activated by L‐α‐lysophosphatidylinositol and various cannabinoid ligands, may regulate endocrine function energy metabolism. We examined how GPR55 deficiency modulation affects insulin signaling in skeletal muscle, adipose tissue, liver alongside expression analysis proteins implicated action show GPR55‐null mice display decreased sensitivity these tissues, as...

Cannabidiol (CBD) is a phytocannabinoid, with anti-apoptotic, anti-inflammatory and antioxidant effects has recently been shown to exert tissue sparing effect during chronic myocardial ischaemia reperfusion (I/R). However, it not known whether CBD cardioprotective in the acute phase of I/R injury present studies tested this hypothesis.Male Sprague-Dawley rats received either vehicle or (10 50 microg kg(-1) i.v.) 10 min before 30 coronary artery occlusion (50 (2 h). The appearance ventricular...

The phospholipid l-α-lysophosphatidylinositol (LPI), an endogenous ligand for GPR55, is elevated in patients with acute coronary syndrome, and a GPR55 antagonist cannabidiol (CBD) reduces experimental ischemia/reperfusion (I/R) injury. While LPI activates multiple signaling pathways, little known about which ones are important cardiomyocytes. In this study we explored whether activation of the Rho kinase/ROCK/p38 MAPK pathway responsible LPI-induced extension I/R Using high-throughput...

Journal Article The antiarrhythmic effect of ischaemic preconditioning in isolated rat heart involves a pertussis toxin sensitive mechanism Get access Lucia Piacentini, Piacentini Cardiovascular Research, Department Physiology and Pharmacology, University Strathclyde, Royal College, 204 Street, Glasgow G1 lXW, United Kingdom: L C Wainwright, J R Parratt. Correspondence to Professor Search for other works by this author on: Oxford Academic PubMed Google Scholar Cherry Wainwright James Parratt...

The effects of intravenous (i.v.) infusions exogenous endothelin-1 (ET-1, 0.05 and 0.1 nmol/kg/min) on incidence severity ventricular arrhythmias during 30-min period acute myocardial ischemia were assessed in anesthetized rats. We examined the role ETA-receptors proarrhythmic both endogenous ET using ETA-receptor antagonist, BQ123. Exogenous ET-1 increased ischemic dose dependently. Both doses total fibrillation (VF: from 30% controls to 100 88% rats given nmol/kg/min ET-1, respectively);...

G protein coupled receptor 55 (GPR55) is expressed throughout the body, and although its exact physiological function unknown, studies have suggested a role in cardiovascular system. In particular, GPR55 has been proposed as mediating haemodynamic effects of number atypical cannabinoid ligands; however this data conflicting. Thus, given incongruous nature our understanding relative paucity literature regarding physiology, study was carried out to examine influence on cardiac function....

The effect of the nitro‐derivative aspirin, NCX4016, was assessed on ischaemic ventricular arrhythmias and myocardial infarct size in anaesthetized pigs comparison to native aspirin. Pigs were given aspirin (10 mg kg −1 ; n =6), low dose NCX4016 (18.4 =6) or high (60 =7) orally for 5 days prior coronary occlusion reperfusion. None interventions had any baseline haemodynamics control ( =9). Aspirin both prevented generation thromboxane A 2 from platelets activated ex vivo with A23187 (30 μ M...

Background Mitogenic stimuli present at the site of coronary arterial balloon injury contribute to progression and development a restenotic lesion, many signaling through common pathway involving small G protein p21 ras . Our aim was demonstrate in biochemical studies that farnesyl transferase inhibitor III (FPTIII) is an processing when it given locally vivo porcine model, can inhibit neointima formation. Methods Results FPTIII (1 25 μmol/L) concentration-dependently reduced levels artery...

The possible role of free radicals in the genesis occlusion and reperfusion‐induced arrhythmias was studied by determining effects xanthine oxidase inhibitor allopurinol (400 mg p.o. 24 h before experimentation + 25 kg −1 i.v.) radical scavenger N‐t‐butyl‐α‐phenyl nitrone (PBN; 50 on these chloralose anaesthetized greyhounds. Neither drugs had any major haemodynamic variables, although caused a significant increase heart rate. mean number extrasystoles observed during ischaemia dogs given or...

Journal Article The effects of PAF antagonists on arrhythmias and platelets during acute myocardial ischaemia reperfusion Get access C. L. WAINWRIGHT, WAINWRIGHT Department Physiology Pharmacology, University StrathclydeGlasgow Scotland U.K. Address for Correspondence: Dr C L Wainwright, Strathclyde, 204 George Street, Glasgow G1 1XW, Scotland, Search other works by this author on: Oxford Academic PubMed Google Scholar J. R. PARRATT, PARRATT M. BIGAUD European Heart Journal, Volume 10, Issue...

Background and Purpose: Protease‐activated receptor‐2 (PAR‐2) is expressed on lymphocytes endothelial cells, plays a significant role in inflammatory reactions. Since leukocyte‐endothelial cell interaction reactive oxygen species (ROS) generation are hallmarks of the development inflammation, effects PAR‐2 activation by trypsin lymphocyte adhesion ROS was examined utilising wild type knockout (PAR‐2−/−) mice. Experimental Approach: Lymphocyte to luminal surface mouse isolated aortae measured...

There are conflicting views in the literature as to whether cannabinoids have an impact on platelet activity and what extent cannabinoid receptors involved. This is important issue resolve because effects of putative therapeutic inhibitors stimulators will their potential benefits safety.The data presented this manuscript clearly show that endocannabinoid 2-arrachidonyl glycerol can activate activity, but mediated through aspirin-sensitive pathway not affected by receptor antagonists or FAAH...

Abstract The receptors mediating the hemodynamic responses to cannabinoids are not clearly defined due multifarious pharmacology of many commonly used cannabinoid ligands. While both CB 1 and TRPV implicated, G protein‐coupled receptor 55 ( GPR 55) may also mediate some effects several atypical present studies attempted unravel underlying in vivo ACEA agonist), O‐1602 AM 251 antagonist), cannabidiol CBD ; antagonist). Agonist antagonist profiles each ligand were determined by ligand‐induced...

The hemodynamic profile and antiarrhythmic properties of pirsidomine, a nitric oxide donor, were examined in pigs. Intravenous administration pirsidomine (1 mg/kg) to chloralose-anesthetized open-chest pigs resulted decreased afterload, reduced myocardial contractility oxygen consumption (assessed by rate-pressure product), with no alterations heart rate. After induction regional ischemia occlusion the left anterior descending coronary artery, given experienced fewer ventricular ectopic...