Abstract:
:1. The pathological features of Gram-positive shock can be mimicked by the co-administration of two cell wall components of Staphylococcus aureus, namely lipoteichoic acid (LTA) and peptidoglycan (PepG). This is associated with the expression of the inducible isoform of nitric oxide synthase (iNOS) in various organs. We have investigated the effects of dexamethasone (which prevents the expression of iNOS protein) or aminoguanidine (an inhibitor of iNOS activity) on haemodynamics, multiple organ dysfunction syndrome (MODS) as well as iNOS activity elicited by LTA + PepG in anaesthetized rats. 2. Co-administration of LTA (3 mg kg-1, i.v.) and PepG (10 mg kg-1, i.v.) resulted in a significant increase in the plasma levels of tumour necrosis factor-alpha (TNF alpha, maximum at 90 min) as well as a biphasic fall in mean arterial blood pressure (MAP) from 120 +/- 3 mmHg (time 0) to 77 +/- 5 mmHg (at 6 h, n = 8; P < 0.05). This hypotension was associated with a significant tachycardia (4-6 h, P < 0.05) and a reduction of the pressor response elicited by noradrenaline (NA, 1 microgram kg-1, i.v., at 1-6 h; n = 8, P < 0.05). Furthermore, LTA + PepG caused time-dependent increases in the serum levels of markers of hepatocellular injury, glutamate-pyruvate-transminase (GPT) and glutamate-oxalacetate-transaminase (GOT). In addition, urea and creatinine (indicators of renal dysfunction) were increased. There was also a fall in arterial oxygen tension (PaO2), indicating respiratory dysfunction, and metabolic acidosis as shown by the significant drop in pH, PaCO2 and HCO3-. These effects caused by LTA + PepG were associated with the induction of iNOS activity in aorta, liver, kidney and lungs as well as increases in serum levels of nitrite+nitrate (total nitrite). 3. Pretreatment of rats with dexamethasone (3 mg kg-1, i.p.) at 120 min before LTA + PepG administration significantly attenuated these adverse effects as well as the increases in the plasma levels of TNF alpha caused by LTA + PepG. The protective effects of dexamethasone were associated with a prevention of the increase in iNOS activity (in aorta, liver, lung, kidney), the expression of iNOS protein (in lungs), as well as in the increase in the plasma levels of total nitrite. 4. Treatment of rats with aminoguanidine (5 mg kg-1 + 10 mg kg-1 h-1) starting at 120 min after LTA + PepG attenuated most of the adverse effects and gave a significant inhibition of iNOS activity (in various organs) as well as an inhibition of the increase in total plasma nitrite. However, aminoguanidine did not improve renal function although this agent caused a substantial inhibition of NOS activity in the kidney. 5. Thus, an enhanced formation of NO by iNOS importantly contributes to the circulatory failure, hepatocellular injury, respiratory dysfunction and the metabolic acidosis, but not the renal failure, caused by LTA + PepG in the anaesthetized rat.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Kengatharan KM,De Kimpe SJ,Thiemermann Cdoi
10.1111/j.1476-5381.1996.tb16053.xsubject
Has Abstractpub_date
1996-12-01 00:00:00pages
1411-21issue
7eissn
0007-1188issn
1476-5381journal_volume
119pub_type
杂志文章abstract::1. In a rat model of experimental ileus, the effect of blockade of adrenergic and nitrergic neurotransmission was studied on the intestinal transit of Evans blue. 2. Ether anaesthesia and skin incision had no influence on the transit. Laparotomy significantly inhibited the transit of Evans blue. This inhibition was ev...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0700913
更新日期:1997-02-01 00:00:00
abstract::(1) Rapid desensitization of ligand-gated ion channel receptors can alter the apparent activity of receptor modulators, as well as make detection of fast-channel activation difficult. Investigation of the antagonist pharmacology of ATP-sensitive homomeric P2X3 receptors is limited by agonist-evoked fast-desensitizatio...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705411
更新日期:2003-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Heparin is known to possess a range of activities, other than effects on blood coagulation, many of which are anti-inflammatory. Effects with potential anti-inflammatory applications include the inhibition of elastase release from neutrophils, as well as the adhesion of these cells to vascular en...
journal_title:British journal of pharmacology
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doi:10.1038/sj.bjp.0707298
更新日期:2007-07-01 00:00:00
abstract::Mast cells participate in allergies, and also in immunity and inflammation by secreting proinflammatory cytokines. Flavonoids are naturally occurring polyphenolic plant compounds, one group of which -- the flavonols, inhibits histamine and some cytokine release from rodent basophils and mast cells. However, the effect...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706246
更新日期:2005-08-01 00:00:00
abstract::1. Caerulein displayed a potent stimulant action on pancreatic secretion in the dog. Threshold doses were 1-5 ng/kg by rapid intravenous injection, 0.25-1 ng/kg per min by intravenous infusion and 50-100 ng/kg by subcutaneous injection. There was a conspicuous increase not only in the volume flow of pancreatic juice b...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb09537.x
更新日期:1969-09-01 00:00:00
abstract::1. The role of nitric oxide in the coronary circulation under basal conditions and when exposed to various vasodilator stimuli was studied in instrumented, anaesthetized goats, by examining the action of inhibiting endogenous nitric oxide production with NG-nitro-L-arginine methyl ester (L-NAME). 2. In 12 goats, left ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14375.x
更新日期:1992-07-01 00:00:00
abstract::1. The affinities of a number of alpha 1-adrenoceptor antagonists were determined by displacement of [3H]-prazosin binding from cloned human alpha 1A-adrenoceptors (previously designated cloned alpha 1c subtype), alpha 1B alpha 1D and rat alpha 1D-adrenoceptors, stably expressed in rat-1 fibroblasts. Functional affini...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb15907.x
更新日期:1995-07-01 00:00:00
abstract::1. Human mast cell tryptase appears to display considerable variation in activating proteinase-activated receptor 2 (PAR(2)). We found tryptase to be an inefficient activator of wild-type rat-PAR(2) (wt-rPAR(2)) and therefore decided to explore the factors that may influence tryptase activation of PAR(2). 2. Using a 2...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704303
更新日期:2001-10-01 00:00:00
abstract:BACKGROUND:Macrophage elastase (MMP-12) is involved in the inflammatory process of chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate in mice the effect of MMP-12 inhibition on the inflammatory process induced by cigarette smoke (CS) or by lipopolysaccharide (LPS) exposure of the air...
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doi:10.1038/bjp.2008.180
更新日期:2008-07-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb10316.x
更新日期:1988-03-01 00:00:00
abstract::Proteinase-activated receptor-2 (PAR-2) is expressed throughout the gastrointestinal tract including the pancreas, and may be involved in digestive functions. The aim of our study was to evaluate a potential role for PAR-2 in regulating salivary and pancreatic exocrine secretion in vivo. PAR-2-activating peptides (PAR...
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0703274
更新日期:2000-04-01 00:00:00
abstract::1. The aim of this study was to investigate whether the hypotensive effect of rat alpha-calcitonin gene-related peptide (alpha CGRP) in conscious rats is mediated by endothelium-derived nitric oxide (NO) or the opening of adenosine 5'-triphosphate (ATP)-sensitive potassium (KATP) channels. 2. Dose-mean arterial pressu...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14290.x
更新日期:1992-05-01 00:00:00
abstract::1. The effects of the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) on the ionic currents of rat carotid body type I cells were investigated by use of whole-cell and outside-out patch clamp techniques. 2. NDGA (5-50 microM) produced a concentration-dependent inhibition of whole-cell K+ currents at all activa...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701452
更新日期:1997-11-01 00:00:00
abstract::1. gamma-Aminobutyric acid (GABA) was applied by the 'concentration clamp' technique to isolated neurones of Aplysia. GABA induced a chloride current (ICl) due to activation of a single class of chloride-channel. 2. The concentration-response curve for the peak ICl gave an apparent dissociation constant of 6.4 X 10(-5...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11718.x
更新日期:1988-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Insulin stimulates the transport of glucose in target tissues by triggering the translocation of glucose transporter 4 (GLUT4) to the plasma membrane. Resistance to insulin, the major abnormality in type 2 diabetes, results in a decreased GLUT4 translocation efficiency. Thus, special attention is...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12845
更新日期:2014-12-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb16445.x
更新日期:1984-05-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb09687.x
更新日期:1974-09-01 00:00:00
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更新日期:2001-01-01 00:00:00
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更新日期:2011-07-01 00:00:00
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更新日期:2001-09-01 00:00:00
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0700959
更新日期:1997-03-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb08823.x
更新日期:1985-05-01 00:00:00
abstract::1 Tissue was taken from guinea-pigs that had been injected with guanethidine (100 mg/kg, i.p.) 24 h before they were killed, and from paired control animals.2 Pretreatment with guanethidine caused a significant, substantial, and sometimes complete reduction of the nerve-mediated contractions of the vas deferens. There...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb09593.x
更新日期:1974-01-01 00:00:00
abstract::1. We have studied the effect of cannabinoid agonists (CP 55,940 and cannabinol) on intestinal motility in a model of intestinal inflammation (induced by oral croton oil in mice) and measured cannabinoid receptor expression, endocannabinoids (anandamide and 2-arachidonylglycerol) and anandamide amidohydrolase activity...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:2001-10-01 00:00:00
abstract::1. An antisense approach to block nitric oxide (NO) synthesis was developed, complementing the widely used chemical inhibitors and overcoming problems associated with their use in studying the roles of NO. 2. Murine macrophage cell lines (J774.2) were generated expressing a 500 bp sequence from inducible NO synthase (...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:1997-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:A non-psychoactive phytocannabinoid, cannabidiol (CBD), shows promising results as an effective potential antiepileptic drug in some forms of refractory epilepsy. To elucidate the mechanisms by which CBD exerts its anti-seizure effects, we investigated its effects at synaptic connections and on t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:2018-06-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704075
更新日期:2001-06-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 社论
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更新日期:2010-03-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb17186.x
更新日期:1995-02-01 00:00:00
abstract::1. The effects of the selective alpha 2-adrenoceptor agonist, medetomidine, were assessed on plasma levels of immunoreactive atrial natriuretic peptide (IR-ANP), haemodynamics and on urine water and solute excretion in conscious, chronically cannulated, 7 month-old spontaneously hypertensive (SHR) and age-matched Wist...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb11932.x
更新日期:1989-05-01 00:00:00