Chronic inhibition of fatty acid amide hydrolase by URB597 produces differential effects on cardiac performance in normotensive and hypertensive rats.

Abstract:

BACKGROUND AND PURPOSE:Fatty acid amide hydrolase (FAAH) inhibitors are postulated to possess anti-hypertensive potential, because their acute injection decreases BP in spontaneously hypertensive rats (SHR), partly through normalization of cardiac contractile function. Here, we examined whether the potential hypotensive effect of chronic FAAH inhibition by URB597 in hypertensive rats correlated with changes in cardiac performance. EXPERIMENTAL APPROACH:Experiments were performed using perfused hearts and left atria isolated from 8- to 10-week-old SHR, age-matched deoxycorticosterone acetate (DOCA)-salt rats and normotensive controls chronically treated with URB597 (1 mg·kg-1 ) or vehicle. KEY RESULTS:URB597 decreased BP only in the DOCA-salt rats, along with a reduction of ventricular hypertrophy and diastolic stiffness, determined in hypertension. We also observed normalization of the negative inotropic atrial response to the cannabinoid receptor agonist CP55940. In the SHR model, URB597 normalized (atria) and enhanced (hearts) the positive ino- and chronotropic effects of the β-adrenoceptor agonist isoprenaline respectively. Ventricular CB1 and CB2 receptor expression was decreased only in the DOCA-salt model, whereas FAAH expression was reduced in both models. URB597 caused translocation of CB1 receptor immunoreactivity to the intercalated discs in the hearts of SHR. URB597 increased cardiac diastolic stiffness and modified the ino- and lusitropic effects of isoprenaline in normotensive rats. CONCLUSION AND IMPLICATIONS:Hypotensive effect of chronic FAAH inhibition depend on the model of hypertension and partly correlate with improved cardiac performance. In normotensive rats, chronic FAAH inhibition produced several side-effects. Thus, the therapeutic potential of these agents should be interpreted cautiously.

journal_name

Br J Pharmacol

authors

Pędzińska-Betiuk A,Weresa J,Toczek M,Baranowska-Kuczko M,Kasacka I,Harasim-Symbor E,Malinowska B

doi

10.1111/bph.13830

subject

Has Abstract

pub_date

2017-07-01 00:00:00

pages

2114-2129

issue

13

eissn

0007-1188

issn

1476-5381

journal_volume

174

pub_type

杂志文章
  • Influence of dopamine as noradrenaline precursor on the secretory function of the bovine corpus luteum in vitro.

    abstract::1. Dopamine is assumed to affect the ovary function after its conversion into noradrenaline (NA). 2. To study this bovine luteal slices from 11-14 days of the oestrous cycle were preincubated for 24 h to recover beta-receptors and next they were incubated for 1, 2 or 4 h with (a) different doses of dopamine; (b) dopam...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1996.tb15590.x

    authors: Kotwica J,Skarzynski D,Bogacki M,Miszkiel G

    更新日期:1996-08-01 00:00:00

  • Blockade of intracellular actions of calcium may protect against ischaemic damage to the gerbil brain.

    abstract::1. The brain cytoprotective effects of a putative calcium-associated protein kinase inhibitor, HA1077, as well as a calcium entry blocker nicardipine were evaluated in models of cerebral ischaemia in Mongolian gerbils. Morphological changes characterizing delayed neuronal death of selectively vulnerable CA1 pyramidal ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1991.tb12355.x

    authors: Asano T,Ikegaki I,Satoh S,Mochizuki D,Hidaka H,Suzuki Y,Shibuya M,Sugita K

    更新日期:1991-08-01 00:00:00

  • Changes in the cytosolic Ca2+ concentration and Ca(2+)-sensitivity of the contractile apparatus during angiotensin II-induced desensitization in the rabbit femoral artery.

    abstract::1. To investigate the underlying mechanism for the angiotensin II-induced desensitization of the contractile response during the prolonged stimulation of the vascular smooth muscle, we determined the effects of angiotensin-II on (1) cytosolic Ca2+ concentration ([Ca2+]i) and tension using fura-2-loaded medial strips o...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0703092

    authors: Ushio-Fukai M,Yamamoto H,Toyofuku K,Nishimura J,Hirano K,Kanaide H

    更新日期:2000-02-01 00:00:00

  • The novel anticonvulsant MK-801 binds to the activated state of the N-methyl-D-aspartate receptor in rat brain.

    abstract::The influence of endogenous and exogenous acidic amino acids on the binding of [3H]-MK-801, a selective, non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, has been investigated in rat cerebral cortex crude synaptic membranes (CSM). Removal of endogenous glutamate and aspartate from CSM by repeated w...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1987.tb10295.x

    authors: Foster AC,Wong EH

    更新日期:1987-06-01 00:00:00

  • Activation of PPAR-δ induces microRNA-100 and decreases the uptake of very low-density lipoprotein in endothelial cells.

    abstract:BACKGROUND AND PURPOSE:Increased level of very low-density lipoprotein (VLDL) is a key feature of the metabolic syndrome and is associated with cardiovascular diseases. PPAR-δ agonists play a protective role in lipid metabolism and vascular function. In this study, we aimed to investigate the role of PPAR-δ in the upta...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/bph.13160

    authors: Fang X,Fang L,Liu A,Wang X,Zhao B,Wang N

    更新日期:2015-08-01 00:00:00

  • Evidence of a role for NK1 and CGRP receptors in mediating neurogenic vasodilatation in the mouse ear.

    abstract::The aims of this study were to develop a technique to measure blood flow in the mouse ear and to investigate the nature of the vasodilator mediator(s) involved in the response to capsaicin. The response to capsaicin, applied topically, was investigated in anaesthetized CD1 or Sv129+C57BL/6 wild-type (+/+) or NK(1) rec...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0704485

    authors: Grant AD,Gerard NP,Brain SD

    更新日期:2002-01-01 00:00:00

  • Ryanodine prolongs Ca-currents while suppressing contraction in rat ventricular muscle cells.

    abstract::Ryanodine (1 microM) suppressed or abolished contraction in response to step depolarization in voltage-clamped cells isolated from adult rat ventricular myocardium. The step depolarizations evoked the second inward current, which is carried largely by Ca ions under these conditions, and there was little or no change i...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1984.tb10735.x

    authors: Mitchell MR,Powell T,Terrar DA,Twist VW

    更新日期:1984-01-01 00:00:00

  • Rhythmic relaxations of active tension in the rabbit large arteries induced by a combination of cyclopiazonic acid and Bay K 8644.

    abstract::1. We previously demonstrated that cyclopiazonic acid (CPA), an inhibitor of Ca(2+)-ATPase in the sarcoplasmic reticulum, induced rhythmic relaxations of active tension in the endothelium-denuded small arteries of the mesentery and the ear of the rabbit, but that this agent failed to induce rhythmic responses in the e...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1996.tb15392.x

    authors: Omote M,Mizusawa H

    更新日期:1996-05-01 00:00:00

  • Hydrogen sulfide causes vanilloid receptor 1-mediated neurogenic inflammation in the airways.

    abstract::Hydrogen sulfide (H(2)S) is described as a mediator of diverse biological effects, and is known to produce irritation and injury in the lung following inhalation. Recently, H(2)S has been found to cause contraction in the rat urinary bladder via a neurogenic mechanism. Here, we studied whether sodium hydrogen sulfide ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0706277

    authors: Trevisani M,Patacchini R,Nicoletti P,Gatti R,Gazzieri D,Lissi N,Zagli G,Creminon C,Geppetti P,Harrison S

    更新日期:2005-08-01 00:00:00

  • Modulation by protease-activated receptors of the rat duodenal motility in vitro: possible mechanisms underlying the evoked contraction and relaxation.

    abstract::1 The present study examined effects of agonist enzymes and receptor-activating peptides for protease-activated receptors (PARs) on duodenal motility in the rat, and also investigated possible mechanisms underlying the evoked responses. 2 Thrombin at 0.03-0.1 microM and the PAR-1-activating peptide SFLLR-NH2 at 3-100 ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0702755

    authors: Kawabata A,Kuroda R,Nishikawa H,Kawai K

    更新日期:1999-10-01 00:00:00

  • G protein-coupled oestrogen receptor 1 (GPER1)/GPR30: a new player in cardiovascular and metabolic oestrogenic signalling.

    abstract::Oestrogens are important sex hormones central to health and disease in both genders that have protective effects on the cardiovascular and metabolic systems. These hormones act in complex ways via both genomic and non-genomic mechanisms. The genomic mechanisms are relatively well characterized, whereas the non-genomic...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1476-5381.2011.01235.x

    authors: Nilsson BO,Olde B,Leeb-Lundberg LM

    更新日期:2011-07-01 00:00:00

  • Evidence for a GABA(B) receptor component in the spinal action of Substance P (SP) on arterial blood pressure in the awake rat.

    abstract::1 The activation of tachykinin NK(1) receptors in the rat spinal cord produced a transient drop in arterial blood pressure followed by a more prolonged pressor effect which is mediated by the stimulation of the sympatho-adrenal system. This study aims at characterizing the spinal mechanism of that initial hypotension ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0704813

    authors: Brouillette J,Couture R

    更新日期:2002-08-01 00:00:00

  • Incorporation of sodium channel blocking and free radical scavenging activities into a single drug, AM-36, results in profound inhibition of neuronal apoptosis.

    abstract::AM-36 is a novel neuroprotective agent incorporating both antioxidant and Na(+) channel blocking actions. In cerebral ischaemia, loss of cellular ion homeostasis due to Na(+) channel activation, together with increased reactive oxygen species (ROS) production, are thought to contribute to neuronal death. Since neurona...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0704018

    authors: Callaway JK,Beart PM,Jarrott B,Giardina SF

    更新日期:2001-04-01 00:00:00

  • Receptors for neurotransmitters in opossum oesophagus muscularis mucosa.

    abstract::Muscularis mucosa of the distal oesophagus of the opossum contains nerves which release acetylcholine and substance P(SP)-like material on field stimulation. The release of SP-like material appeared to be inhibited by the presence of exogenous muscarinic agonists and potentiated by muscarinic antagonists. Analysis of ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1986.tb10254.x

    authors: Daniel EE,Jury J,Robotham KH

    更新日期:1986-07-01 00:00:00

  • The acute effects of dimebolin, a potential Alzheimer's disease treatment, on working memory in rhesus monkeys.

    abstract:BACKGROUND:Dimebolin (latrepirdine), a compound with multiple potential drug targets, is being evaluated in clinical trials for the treatment of Alzheimer's disease (AD) and preliminary results suggest it can slow the disease process. There is also evidence that dimebolin directly improves aspects of cognition. Here we...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.2011.01432.x

    authors: Webster SJ,Wilson CA,Lee CH,Mohler EG,Terry AV Jr,Buccafusco JJ

    更新日期:2011-10-01 00:00:00

  • Effects of sodium and calcium concentrations on the potentiation by indomethacin of the responses of rabbit mesenteric and coeliac arteries to vasoconstrictor agonists.

    abstract::The contractile responses of the rabbit isolated coeliac and mesenteric arteries to five agonists (angiotensin, adrenaline, histamine, acetylcholine and 5-hydroxytryptamine), but not to K+, were potentiated by indomethacin (8.4 microM) The potentiation was similar whether indomethacin was added 1 h before or during th...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1983.tb10714.x

    authors: Novelli EL,Oshiro ME,Paiva AC,Paiva TB

    更新日期:1983-11-01 00:00:00

  • Caffeine-induced decreases in the inward rectifier potassium and the inward calcium currents in rat ventricular myocytes.

    abstract::The effects of high (20 mM) concentrations of caffeine were studied on the transmembrane voltage and currents in rat single ventricular myocytes by the whole cell configuration of the patch clamp technique. Rapid application of caffeine released Ca2+ from the sarcoplasmic reticulum and induced a Ni(2+)-sensitive trans...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1993.tb13702.x

    authors: Varro A,Hester S,Papp JG

    更新日期:1993-08-01 00:00:00

  • Distinct PKC isoforms mediate the activation of cPLA2 and adenylyl cyclase by phorbol ester in RAW264.7 macrophages.

    abstract::The modulatory effects of protein kinase C (PKC) on the activation of cytosolic phospholipase A2 (cPLA2) and adenylyl cyclase (AC) have recently been described. Since the signalling cascades associated with these events play critical roles in various functions of macrophages, we set out to investigate the crosstalk be...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0702219

    authors: Lin WW,Chen BC

    更新日期:1998-12-01 00:00:00

  • Actions of baclofen on components of the Ca-current in rat and mouse DRG neurones in culture.

    abstract::1. Ca currents in rat and mouse sensory dorsal root ganglion (DRG) neurones were inhibited by concentrations of (-)-baclofen as low as 1 micron. The proportion of neurones responding to baclofen was low (less than 20%), except in young cultures of neonate rat DRG neurones (3 days in culture), where 86% of the neurones...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1988.tb11520.x

    authors: Green KA,Cottrell GA

    更新日期:1988-05-01 00:00:00

  • An in vivo role for Rho kinase activation in the tumour vascular disrupting activity of combretastatin A-4 3-O-phosphate.

    abstract:BACKGROUND AND PURPOSE:Combretastatin A-4 3-O-phosphate (CA4P) is in clinical trial as a tumour vascular disrupting agent (VDA) but the cause of blood flow disruption is unclear. We tested the hypothesis that activation of Rho/Rho kinase (ROCK) is fundamental to the effects of this drug in vivo. EXPERIMENTAL APPROACH:...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/bph.12817

    authors: Williams LJ,Mukherjee D,Fisher M,Reyes-Aldasoro CC,Akerman S,Kanthou C,Tozer GM

    更新日期:2014-11-01 00:00:00

  • Brain alpha(2)-adrenoceptors in monoamine-depleted rats: increased receptor density, G coupling proteins, receptor turnover and receptor mRNA.

    abstract::1. This study was designed to assess the molecular and cellular events involved in the up-regulation (and receptor supersensitivity) of brain alpha(2)-adrenoceptors as a result of chronic depletion of noradrenaline (and other monoamines) by reserpine. 2. Chronic reserpine (0.25 mg kg(-1) s.c., every 48 h for 6 - 14 da...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0703963

    authors: Ribas C,Miralles A,Busquets X,García-Sevilla JA

    更新日期:2001-04-01 00:00:00

  • Studies on the effect of MDMA ('ecstasy') on the body temperature of rats housed at different ambient room temperatures.

    abstract::3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') administration to rats produces hyperthermia if they are housed in normal or warm ambient room temperature (Ta) conditions (>or=20 degrees C), but hypothermia when in cool conditions (Ta

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0706318

    authors: Green AR,O'Shea E,Saadat KS,Elliott JM,Colado MI

    更新日期:2005-09-01 00:00:00

  • Resistance to myocardial infarction induced by heat stress and the effect of ATP-sensitive potassium channel blockade in the rat isolated heart.

    abstract::1. Heat stress (HS) is known to protect against myocardial ischaemia-reperfusion injury by improving mechanical dysfunction and decreasing necrosis. However, the mechanisms responsible for this form of cardioprotection remain to be elucidated. ATP-sensitive potassium (K(ATP)) channels have been shown to be involved in...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0701710

    authors: Joyeux M,Godin-Ribuot D,Ribuot C

    更新日期:1998-03-01 00:00:00

  • Actions of cocaine on rat dopaminergic neurones in vitro.

    abstract::1. Intracellular recordings were made from neurones in vitro in the rat substantia nigra zona compacta and ventral tegmental area; the neurones had the characteristic properties of dopamine-containing cells, and fired action potentials spontaneously. 2. Cocaine (1-10 microM) inhibited spontaneous firing, hyperpolarize...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1990.tb12998.x

    authors: Lacey MG,Mercuri NB,North RA

    更新日期:1990-04-01 00:00:00

  • Antileukoproteinase protects against hepatic inflammation, but not apoptosis in the response of D-galactosamine-sensitized mice to lipopolysaccharide.

    abstract:BACKGROUND AND PURPOSE:There is major evidence for the strong bi-directional interrelation of parenchymal cell apoptosis and leukocyte accumulation and inflammation in acute liver injury. Therefore, the aim of this in vivo study was to investigate the anti-apoptotic and anti-inflammatory potential of antileukoproteinas...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0707230

    authors: Eipel C,Kidess E,Abshagen K,Leminh K,Menger MD,Burkhardt H,Vollmar B

    更新日期:2007-06-01 00:00:00

  • A study of tolerance to apomorphine.

    abstract::1. The present study was designed to investigate tolerance to several pharmacological effects of apomorphine. 2. Changes in blood pressure, heart rate, plasma noradrenaline levels, rectal temperature, respiratory rate and retching plus vomiting were compared after administration of apomorphine (200 micrograms kg-1, i....

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1996.tb15260.x

    authors: Montastruc JL,Llau ME,Senard JM,Tran MA,Rascol O,Montastruc P

    更新日期:1996-03-01 00:00:00

  • Effects of halothane on the membrane potential in skeletal muscle of the frog.

    abstract::Halothane has many effects on the resting membrane potential (V(m)) of excitable cells and exerts numerous effects on skeletal muscle one of which is the enhancement of Ca(2+) release by the sarcoplasmic reticulum (SR) resulting in a sustained contracture. The aim of this study was to analyse the effects of clinical d...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0703330

    authors: Sauviat MP,Frizelle HP,Descorps-Declère A,Mazoit JX

    更新日期:2000-06-01 00:00:00

  • Rho-kinase inhibitors prevent agonist-induced vasospasm in human internal mammary artery.

    abstract::1. Vasospasm of arterial conduits used for coronary artery surgery is an important cause of graft failure and is likely to result partly from raised levels of vasoconstrictor substances such as thromboxane A(2) and endothelin-1. Our aim was to find pharmacological agents that could prevent agonist-induced vasospasm. 2...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0703809

    authors: Batchelor TJ,Sadaba JR,Ishola A,Pacaud P,Munsch CM,Beech DJ

    更新日期:2001-01-01 00:00:00

  • Morphine dependence and dopaminergic activity: tests of circling responses in rats with unilateral nigral lesions.

    abstract::1 Rats with unilateral electrolytic lesions involving both parts of the substantia nigra show dose-related, ipsilateral circling responses to apomorphine which are stable over time. 2 In non-tolerant rats, morphine (up to 10 mg/kg) does not elicit any circling behaviour but as tolerance develops to morphine, initially...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1980.tb09773.x

    authors: Halliwell JV,Kumar R

    更新日期:1980-12-01 00:00:00

  • Selective inhibition of human inducible nitric oxide synthase by S-alkyl-L-isothiocitrulline-containing dipeptides.

    abstract::The aim of this study was to investigate the structure-activity relationship of S-alkyl-L-isothiocitrulline-containing dipeptides towards three partially purified recombinant human nitric oxide synthase (NOS) isozymes, as well as the effects of these compounds on cytokine-induced NO production by human DLD-1 cells. In...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0704023

    authors: Park JM,Higuchi T,Kikuchi K,Urano Y,Hori H,Nishino T,Aoki J,Inoue K,Nagano T

    更新日期:2001-04-01 00:00:00