Abstract：
BACKGROUND AND PURPOSE:NO-mediated, endothelium-dependent relaxations of isolated arteries are blunted by ageing and high-fat diets, as well as by apolipoprotein E deletion. The present study was designed to test the hypothesis that apolipoprotein E deletion impairs endothelium-dependent responses to prostacyclin (IP) receptor activation. EXPERIMENTAL APPROACH:Five-week-old ApoE+/+ and ApoE-/- mice were fed normal chow or high-fat diet for 29 weeks. The aortae were isolated for the measurements of isometric tension in Halpern-Mulvany myographs. Levels of proteins were assessed by Western blotting and immunofluorescence, and cyclic nucleotide levels by elisa. KEY RESULTS:The IP receptor agonist, iloprost, induced endothelium-, NO-synthase- and IP-dependent relaxations in aortae of young ApoE+/+ mice. High-fat diet favoured activation of thromboxane receptors by iloprost, causing contraction. Apolipoprotein E was present in aortae of ApoE+/+ mice, especially in endothelium. Its presence was augmented by high-fat diet. Its deletion potentiated iloprost-induced relaxations in aortae of young mice and prevented the blunting of this response by high-fat diet. Levels of cAMP were higher, but those of cGMP were lower in the aorta of ApoE-/- than in ApoE+/+ mice of the same age. The levels of IP receptor protein were not different between ApoE+/+ and ApoE-/- mice. CONCLUSIONS AND IMPLICATIONS:Iloprost induced an endothelium-dependent relaxation in the aorta of young healthy mice which involved both the cGMP and cAMP pathways. This response was blunted by prolonged exposure to a high-fat diet. Apolipoprotein E deletion potentiated relaxations to IP receptor activation, independently of age and diet.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Cheng Y,Vanhoutte PM,Leung SWSdoi
10.1111/bph.14386subject
Has Abstractpub_date
2018-09-01 00:00:00pages
3453-3469issue
17eissn
0007-1188issn
1476-5381journal_volume
175pub_type
杂志文章abstract：:The effects of dopamine receptor and alpha-adrenoceptor agonists and antagonists on the stimulation-evoked overflow of radioactivity from strips of dog saphenous vein previously loaded with [3H]-noradrenaline have been examined alone and in combination. In the presence of neuronal and extraneuronal catecholamine uptak...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1984.tb10098.x
更新日期：1984-03-01 00:00:00
abstract：:1. A wide panel of compounds acting on beta-adrenoceptors active either in mammalian heart or in rodent digestive tract and adipose tissues, were investigated for their effects on Chinese hamster ovary cells transfected with the human or murine beta 3-adrenoceptor gene. 2. The beta 3-agonists, bucindolol, CGP 12177A a...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb13167.x
更新日期：1994-07-01 00:00:00
abstract：:1 Pretreatment of dogs for 20 to 24 h before the start of experiments with reserpine (0.5 mg/kg) depleted noradrenaline from cerebral and mesenteric arteries, the diminution being greater in the latter arteries. 2 Contractile responses of helically-cut strips of cerebral and mesenteric arteries to noradrenaline were u...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1980.tb14561.x
更新日期：1980-03-01 00:00:00
abstract：:1. In this study, we compared two series of newly discovered ligands for their selectivity to benzodiazepine sites in the alpha 1 beta 2 gamma 2 and the alpha 6 beta 2 gamma 2 subtypes of cloned gamma-aminobutyric acidA (GABAA) receptors, the latter being unique in not interacting with classical benzodiazepines. 2. Th...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13864.x
更新日期：1993-10-01 00:00:00
abstract：:1. The present study characterized highly effective agonists from different classes of compounds for the neuronal octopamine receptor (OAR3) of the migratory locust (Locusta migratoria L.). Biogenic amines and phenyliminoimidazolidines (PIIs) were employed for the study of structure-activity relationships. 2. The high...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb14927.x
更新日期：1995-01-01 00:00:00
abstract：:1. The influence of different holding potentials (-120 to -70 mV) on the contraction of enzymatically dispersed myocytes from guinea-pig hearts was evaluated. Contractions were elicited by repetitive depolarizations to 0 mV at 0.5 Hz. 2. While ineffective at 140 and 5 mmol l-1 [Na+]o and pipette Na+, respectively, dep...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12492.x
更新日期：1991-11-01 00:00:00
abstract：:1. Morphine-like analgesic drugs caused depression of twitches of the isolated guinea-pig ileum in response to transmural electrical stimulation. The drugs tested were the narcotic analgesics codeine, diamorphine, fentanyl, morphine, morphine-N-oxide, normorphine, oxymorphone, pethidine, phenazocine and phenoperidine ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1969.tb10580.x
更新日期：1969-10-01 00:00:00
abstract：:1. The chemically novel acetohydroxamic acids, BW A4C, BW A137C and BW A797C, are potent inhibitors of the synthesis of leukotriene B4 (LTB4) from arachidonic acid by human leucocyte homogenates: the concentrations required for 50% inhibition (IC50) were 0.1 microM, 0.8 microM and 0.5 microM respectively. Inhibition w...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11557.x
更新日期：1988-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:5alpha,8alpha-Epidioxy-22E-ergosta-6, 22-dien-3beta-ol (ergosterol peroxide) is a major antitumour sterol produced by edible or medicinal mushrooms. However, its molecular mechanism of action has yet to be determined. Here, we examine the anticancer and anti-inflammatory effects of ergosterol per...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706972
更新日期：2007-01-01 00:00:00
abstract：:1 The response of pentobarbitone-anaesthetized cats to the intravenous administration of E. coli endotoxin (2 mg/kg) consisted of acute pulmonary vasoconstriction (3-5 min after the injection) and a secondary shock phase characterized by delayed systemic hypotension, decreased central venous pressure and cardiac outpu...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1974.tb08559.x
更新日期：1974-02-01 00:00:00
abstract：:1. Ca2+ buffering function of sarcoplasmic reticulum (SR) in the resting state of arteries from spontaneously hypertensive rats (SHR) was examined. Differences in the effects of cyclopiazonic acid (CPA) and thapsigargin, agents which inhibit the Ca(2+)-ATPase of SR, on tension and cellular Ca2+ level were assessed in ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0700857
更新日期：1997-01-01 00:00:00
abstract：:1. Muscarinic receptors on endothelial cells of bovine thoracic aorta were characterized by binding assays in which (-)-[3H]-N-methyl quinuclidinyl benzilate ([3H]-NMeQNB) was used as radioligand. 2. Binding of [3H]-NMeQNB to crude membranes of freshly isolated endothelial cells was atropine-displaceable and of high a...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12181.x
更新日期：1991-02-01 00:00:00
abstract：:1. The endothelium-dependent relaxants acetylcholine (ACh; 0.03-10 microM) and A23187 (0.03-10 microM), and nitric oxide (NO), applied either as authentic NO (0.01-10 microM) or as the NO donors 3-morpholino-sydnonimine (SIN-1; 0.1-10 microM) and S-nitroso-N-acetylpenicillamine (SNAP; 0.1-10 microM), each evoked conce...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701746
更新日期：1998-04-01 00:00:00
abstract：:Peroxynitrite, a potent oxidant formed by the reaction of nitric oxide and superoxide causes thymocyte necrosis, in part, via activation of the nuclear enzyme poly(ADP-ribose) synthetase (PARS). The cytotoxic PARS pathway initiated by DNA strand breaks and excessive PARS activation has been shown to deplete cellular e...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702332
更新日期：1999-02-01 00:00:00
abstract：:1. The receptor for glucagon-like peptide-1 (GLP-1) can be activated by both its physiological hormone and a peptide discovered in the venom of the Gila Monster, exendin-4, which shows promise as an antidiabetic agent. 2. Exendin-4 displays receptor-binding properties not observed for GLP-1. Firstly, exendin-4 can be ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705453
更新日期：2003-09-01 00:00:00
abstract：:1. The regional binding of [3H]-(+)-5-methyl-10,11-dihydro-5H-dibenzo (a,d)cyclohepten-5,10-imine maleate ([3H]-(+)-MK 801) to sections of rat brain was measured by an in vitro quantitative autoradiographic technique. A heterogeneous distribution of binding sites was observed. 2. High values of binding were detected i...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb12845.x
更新日期：1993-03-01 00:00:00
abstract：:1 The effect of thiopentone, methohexitone, urethane and ketamine on the uptake and release of gamma-aminobutyric acid (GABA) and D-aspartate by rat thalamic slices has been investigated. 2 A high, supra-anaesthetic concentration of methohexitone increased the uptake of both D-aspartate and GABA. 3 None of the anaesth...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1982.tb08776.x
更新日期：1982-01-01 00:00:00
abstract：:1. Tyramine 10(-4)M significantly increased release of noradrenaline-7-(3)H (NA-7-(3)H) from rat vas deferens in vitro.2. Neither cocaine 10(-5)M nor imipramine 10(-7)M-10(-6)M significantly reduced tyramine-induced release of NA-7-(3)H.3. Increasing the exposure time to cocaine and imipramine from 10 to 20 min or pre...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1969.tb08305.x
更新日期：1969-05-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The sodium channel is a primary target for treating central nervous system disorders such as epilepsy. In this study the anticonvulsant effect of BmK IT2, a sodium channel-specific neurotoxin, was evaluated in different animal models of epilepsy. EXPERIMENTAL APPROACH:Experiments were performed ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/bjp.2008.156
更新日期：2008-07-01 00:00:00
abstract：:1. The effects of low oxygen tension on tone and on the responsiveness to contractile and relaxant agents were examined on circumflex coronary artery rings isolated from sheep. 2. When artery rings (2-2.5 mm o.d.) were set at their optimal resting tension, introduction of hypoxia (0% O2) caused a sustained contraction...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb11894.x
更新日期：1989-04-01 00:00:00
abstract：:1. Treatment of rat mesangial cells with interleukin 1 beta (IL-1 beta) or tumour necrosis factor alpha (TNF alpha) has been shown to induce a macrophage-type of nitric oxide (NO) synthase. Here we report that adenosine 3':5'-cyclic monophosphate (cyclic AMP) is another mediator that triggers induction of NO synthase ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb13019.x
更新日期：1994-05-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Sildenafil is a selective inhibitor of cGMP-specific phosphodiesterase. Sildenafil, acting via NO-dependent mechanisms, prevents indomethacin-induced gastropathy. Activation of ATP-sensitive potassium channels (K(ATP)) is involved in gastric defence. Our objective was to evaluate the role of the ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707605
更新日期：2008-02-01 00:00:00
abstract：:1 The concentrations of p- and m-tyramine were measured in the caudate nucleus of the rat brain following subcutaneous injection of reserpine or intraventricular injection of 6-hydroxydopamine, beta-Phenylethylamine was analysed in the hypothalamus after reserpine. 2 Endogenous levels of p-tyramine and m-tyramine in t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1977.tb06996.x
更新日期：1977-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The Na+/Ca2+ exchanger (NCX) may contribute to triggered activity and transmural dispersion of repolarization, which are substrates of torsades de pointes (TdP) type arrhythmias. This study examined the effects of selective inhibition of the NCX by SEA0400 on the occurrence of dofetilide-induced ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2008.00096.x
更新日期：2009-03-01 00:00:00
abstract：:1. Vasoconstrictions induced by transmural electrical field stimulation were frequency-dependent from 2 to 32 Hz in the rabbit isolated splenic artery. All contractions were abolished in the presence of tetrodotoxin 1 microM or guanethidine 100 microM. Stimulation at a frequency of more than 32 Hz induced both neuroge...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0700933
更新日期：1997-02-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The function of transporters in peripheral blood mononuclear cells (PBMC) has been characterized, but less is known about cytochrome P450 (CYP) enzyme function in these cells. Given that cytokines are dysregulated in many diseases, the purpose of this work was to assess the impact of cytokines on...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2008.00050.x
更新日期：2009-02-01 00:00:00
abstract：:1. The effects of intravenous administration of two alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) antagonists were studied on responses of single neurones to iontophoretically applied excitatory amino acids. The tests were performed on spinal neurones in alpha-chloralose anaesthetized, spinalized rat...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb13156.x
更新日期：1994-07-01 00:00:00
abstract：:1. Chronic treatment with low doses of the selective monoamine oxidase (MAO) type B inhibitors selegiline [(-)-deprenyl] and rasagiline, causes elevation in extracellular level of 3,4-dihydroxyphenylethylamine (dopamine) in the rat striatum in vivo (Lamensdorf et al., 1996). The present study was carried out to determ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702389
更新日期：1999-02-01 00:00:00
abstract：:Preclinical and clinical data suggest that a modification in GABA(B) receptor expression and function may contribute to the symptoms of major depression and the response to antidepressants. This includes laboratory animal experiments demonstrating that antidepressants modify brain GABA(B) receptor expression and funct...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1476-5381.2010.01004.x
更新日期：2011-01-01 00:00:00
abstract：:1. A series of GABAB receptor antagonists were tested against (+/-)-baclofen for activity on the presynaptic GABAB receptor in the rat vas deferens. 2. All the antagonists tested caused a rightward shift in the concentration-response curve to (+/-)-baclofen. 3. pA2 values calculated from full Schild analysis were as f...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12224.x
更新日期：1991-03-01 00:00:00
