Abstract：
:1. We examined the relationship between oxidant stress and the vasodepressor activity of glyceryl trinitrate (GTN) in vivo, including rapid GTN tolerance development, in 13-week old obese and age-matched lean Zucker rats which had been maintained for 4 weeks on either control diet or diets enriched with the lipophilic, chain-breaking antioxidants vitamin E (0.5% w w(-1)) or probucol (0.5% w w(-1)) or the superoxide anion scavenger tiron (1% w v(-1) in drinking water). 2. The basal plasma level of the isoprostane 8-epi-PGF2alpha, an in vivo marker of lipid peroxidation, was elevated by approximately 5 fold in the obese Zucker rat and markedly reduced by dietary lipophilic antioxidants and depressed by dietary tiron. 3. Vasodepression to bolus does GTN (0.1-100 microg kg(-1) i.v.), but not endothelium-dependent vasodepression to bolus dose acetylcholine (ACh, 0.02-2.0 microg kg(-1) i.v.), was impaired in obese animals and completely restored by dietary antioxidants. 4. Nitrate tolerance developed in vivo during a I h infusion of GTN (40 microg kg(-1) min(-1) i.v.) appeared more severe in obese animals. However, rapid nitrate tolerance was not affected by dietary antioxidants in either the obese or lean Zucker rat. 5. We therefore provide evidence that elevated oxidant stress in the obese Zucker rat is associated with an impairment in nitrate vasodepressor activity. However, our data are not consistent with either a role for oxidant stress in rapid nitrate tolerance development in the anaesthetized Zucker rat or the aggravation of this tolerance by pre-existing oxidant stress.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Laight DW,Kengatharan KM,Gopaul NK,Anggård EE,Carrier MJdoi
10.1038/sj.bjp.0702132subject
Has Abstractpub_date
1998-10-01 00:00:00pages
895-901issue
4eissn
0007-1188issn
1476-5381journal_volume
125pub_type
杂志文章abstract：:1 The cardiovascular effects of the anthelmintic drug diethylcarbamazine citrate (DECC) were examined in cats anaesthetized with pentobarbitone. There were two quite distinct haemodynamic responses, an initial transient hypotension (occurring within 10 s of an intravenous injection) and a pronounced secondary hyperten...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1976.tb07445.x
更新日期：1976-02-01 00:00:00
abstract：:1. Optimal dipeptide and peptidomimetic drug transport across the intestinal mucosal surface is dependent upon the co-operative functional activity of the di/tripeptide transporter hPepT1 and the Na(+)/H(+) exchanger NHE3. The ability of the anti-absorptive enteric neuropeptide VIP (vasoactive intestinal peptide) to m...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705049
更新日期：2003-02-01 00:00:00
abstract：:1 The intravenous infusion of isoprenaline and salbutamol into the greyhound increased heart rate and levels of free fatty acids, lactic acid and glucose. 2 On terminating the infusions of isoprenaline the changes produced declined rapidly but the effects produced by salbutamol were more persistent. When high doses of...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb07345.x
更新日期：1975-02-01 00:00:00
abstract：:1. Adenosine 5'-triphosphate (ATP) is known to augment cardiac contractile activity and cause an increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) in isolated cardiomyocytes. However, no information regarding the ATP-mediated signal transduction in the myocardium in congestive heart failure (CHF) is availab...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705867
更新日期：2005-01-01 00:00:00
abstract：:1. This study describes the effects of hypoxia on relaxing responses and cAMP production induced by the known vasodilator peptides: alphaCGRP, amylin (AMY) and adrenomedullin (AM) on isolated pig coronary arteries in vitro. 2. Hypoxic incubation increased the vasorelaxant effect of alphaCGRP (four-fold; P<0.05), AMY (...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706232
更新日期：2005-07-01 00:00:00
abstract：:1. The effects of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on vasoconstrictor responses to transmural electrical nerve stimulation and noradrenaline were examined in the rabbit isolated renal artery with and without an intact endothelium. In addition, the effect of removing the end...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701141
更新日期：1997-05-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The chemokine receptor CXCR3 directs migration of T-cells in response to the ligands CXCL9/Mig, CXCL10/IP-10 and CXCL11/I-TAC. Both ligands and receptors are implicated in the pathogenesis of inflammatory disorders, including atherosclerosis and rheumatoid arthritis. Here, we describe the molecul...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01660.x
更新日期：2012-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Red blood cells (RBCs) are reservoirs of vasodilatory, antiaggregatory, and antiinflammatory lipid mediators-epoxyeicosatrienoic acids (EETs). This study addresses the formation and release of erythrocyte-derived EETs in response to ATP receptor stimulation that may represent an important mechani...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707311
更新日期：2007-08-01 00:00:00
abstract：:1. In order to define the electrophysiological mechanism(s) responsible for bradykinin (BK)-induced positive inotropic and chronotropic responses in isolated guinea-pig atria, effects of BK on the membrane currents were examined in isolated atrial cells using patch clamp techniques. 2. BK (0.1-1000 nM) increased the L...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702060
更新日期：1998-09-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Strontium ranelate reduces fracture risk in postmenopausal women with osteoporosis. Evidence from non-clinical studies and analyses of bone markers in phase III trials indicate that this is due to an increase in osteoblast formation and a decrease of osteoclastic resorption. The aim of this work ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00305.x
更新日期：2009-08-01 00:00:00
abstract：:1 Neuroprotection has been reported after either activation or blockade of the group I metabotropic glutamate receptor subtype 5 (mGluR5). However, some recent evidence suggests that protection provided by mGluR5 antagonists may reflect their ability to inhibit N-methyl-D-aspartate (NMDA) receptor activity. 2 Here, in...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706219
更新日期：2005-06-01 00:00:00
abstract：:1 The effects of electrical stimulation, changes in external ion concentrations and various drugs on acetylcholine release from the myenteric plexus were measured by bioassay in the presence of physostigmine and by recording the responses of the longitudinal muscle. In preparations from the guinea-pig, the acetylcholi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1978.tb17319.x
更新日期：1978-12-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Cannabidiol (CBD) has emerged as an interesting compound with therapeutic potential in several CNS disorders. However, whether it can modulate synaptic activity in the CNS remains unclear. Here, we have investigated whether CBD modulates synaptic transmission in rat hippocampal cultures and acute...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2010.01015.x
更新日期：2011-01-01 00:00:00
abstract：:1. The effects of nipradilol, a beta-adrenoceptor antagonist which possesses a nitroxy group, on cytosolic Ca2+ concentration ([Ca2+]i), and on tension development were simultaneously measured by front-surface fluorometry and fura-2-loaded strips in the proximal portion of pig coronary arteries. 2. Nipradilol reduced ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15343.x
更新日期：1996-04-01 00:00:00
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
更新日期：2001-04-01 00:00:00
abstract：:1. Nicotine can activate primary afferent nociceptors, one result of which is to increase neurogenic plasma extravasation. In this study we have demonstrated a novel proinflammatory effect of sub-nanomolar nicotine, mediated by peripheral action at sensory neurons. This action is normally masked by adrenal medulla-der...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704031
更新日期：2001-05-01 00:00:00
abstract：:Cartilage destruction is a key characteristic of arthritic disease, a process now widely established to be mediated by metzincins such as MMPs. Despite showing promise in preclinical trials during the 1990s, MMP inhibitors for the blockade of extracellular matrix turnover in the treatment of cancer and arthritis faile...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.14173
更新日期：2019-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Venoms are a rich source of ligands for ion channels, but very little is known about their capacity to modulate G-protein coupled receptor (GPCR) activity. We developed a strategy to identify novel toxins targeting GPCRs. EXPERIMENTAL APPROACH:We studied the interactions of mamba venom fractions...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00532.x
更新日期：2010-01-01 00:00:00
abstract：:Oxidized low density lipoproteins (oxLDL) are thought to play a major role in atherosclerosis. OxLDL act in part through alteration of intracellular signalling pathways in cells of the vascular wall. We recently reported that the EGF receptor (EGFR) signalling pathway is activated by lipid peroxidation products (among...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703981
更新日期：2001-04-01 00:00:00
abstract：:1. The vasodilator responses of isolated intrapulmonary arteries (IPA) to P2-receptor agonists were investigated during adaptation to extrauterine life in the piglet. The effect of pulmonary hypertension on the normal response was determined after exposing newborn animals to chronic hypobaric hypoxia (51 kPa) for 3 da...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702815
更新日期：1999-10-01 00:00:00
abstract：:The aim of this study was to characterize the angiotensin II receptors in isolated uterine arteries from non pregnant and pregnant rats, since it has been reported from binding studies that ovine uterine arteries contain AT2 receptors. Uterine arterial segments were obtained from virgin, non-pregnant and late pregnant...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702210
更新日期：1998-12-01 00:00:00
abstract：:1. Effects of phorbol esters on the cytosolic Ca2+ level ([Ca2+]i) and muscle tension in the intestinal smooth muscle of guinea-pig taenia caeci were examined. 2. 12-Deoxyphorbol 13-isobutyrate (DPB, 1 microM) did not change the [Ca2+]i and tension in resting muscle. 3. In high K(+)-stimulated muscle, 1 microM DPB tra...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13558.x
更新日期：1993-05-01 00:00:00
abstract：:1 Cellulose sulphate, like heparin, prolonged the clotting time in partial thromboplastin time (PTT) assays, inhibited the amidolytic activity of thrombin, was without effect on amidolysis catalysed by activated coagulation factor X(Xa), and potentiated the inhibition of both thrombin and Xa by antithrombin III (AT). ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1980.tb10856.x
更新日期：1980-04-01 00:00:00
abstract：:1. Strength-duration curves for threshold mechanical responses to single transmural stimuli were identical for rat and guinea-pig detrusor. In both species atropine had no effect on the curves, but the curves were shifted to the right by nerve blockade with tetrodotoxin (TTX), and by blockade of P2-purinoceptors with ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb12956.x
更新日期：1990-03-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Treatment with selective oestrogen receptor modulators (SERMs) reduces low-density lipoprotein (LDL) cholesterol levels. We assessed the effect of tamoxifen, raloxifene and toremifene and their combinations with lovastatin on LDL receptor activity in lymphocytes from normolipidaemic and familial ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13016
更新日期：2015-03-01 00:00:00
abstract：:By implanting a Teflon chamber subcutaneously into a sheep a mild aseptic inflammatory lesion was produced from which wound fluid could be sampled daily. The prostaglandin content of this wound fluid was examined. Prostaglandin E2 activity was found in all samples, and a peak was apparent on the fourth or fifth day af...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb07363.x
更新日期：1975-02-01 00:00:00
abstract：:1 Rabbit isolated hearts, perfused by the Langendorff technique, were used to investigate the indirect sympathomimetic effects of 5-hydroxytryptamine (5-HT). Comparisons were made with noradrenaline and with two indirectly acting sympathomimetic agents with entirely different mechanisms of action, tyramine and dimethy...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1976.tb07661.x
更新日期：1976-05-01 00:00:00
abstract：:1 In unanaesthetized cats, the administration of 6-hydroxydopamine (6-OHDA), 750 mug, via the lateral cerebral ventricle produced a pronounced fall in rectal temperature but only a slight fall when repeated 7 days later. At this time hypothalamic noradrenaline concentration had diminished to 4% of control.2 In these a...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1974.tb09648.x
更新日期：1974-06-01 00:00:00
abstract：:1. Following our earlier observations that the tachykinin NK1 receptor antagonist CP-99,994 is an effective anti-emetic in ferrets, we have examined the anti-emetic effects of a more potent and novel NK1 receptor antagonist, GR203040, against various emetic stimuli in the ferret, dog and house musk shrew (Suncus murin...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb15118.x
更新日期：1995-12-01 00:00:00
abstract：:The mechanism underlying the LTC(4)-induced contraction of guinea-pig taenia coli was determined using the simultaneous measurements of [Ca(2+)](i) and force in whole muscle preparations. Additional experiments were performed in receptor coupled permeabilized preparation. For comparison purposes, the contraction which...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704122
更新日期：2001-06-01 00:00:00
