Abstract:
:We have characterized the contribution of endothelial nitric oxide synthase (eNOS), cyclo-oxygenase (COX) and cytochrome P450 (CYP450) to the bradykinin (BK)- induced vasodilation in isolated hearts from wildtype (WT) and eNOS deficient mice (eNOS-/-). The endothelium-dependent vasodilation by bradykinin (BK, 1 microM) was significantly lower in eNOS-/- hearts than that in WT hearts (+247% and +325% of basal flow, respectively), while there was no difference in the endothelium-independent vasodilation by adenosine. In WT hearts, the BK-induced vasodilation was markedly attenuated following inhibition of NOS with ETU (10 microM) but not after COX inhibition with diclofenac (3 microM) (P<0.01). In line with this finding, Bk did not increase the cardiac prostacyclin release as measured by ELISA for 6-keto-PGF1alpha in the coronary venous effluent. In eNOS-/- hearts, the flow response to BK was insensitive to both NOS and COX inhibition. The NOS/COX-independent vasodilatory factor which remained under L-NMMA+DF application was almost completely eliminated by either clotrimazole (3 microM), miconazole (0.5 microM) or 17-ODYA (1 microM), suggesting that it was a metabolite of CPY450 enzymes. Sulfaphenazole (10 microM), a CYP450 2C inhibitor, exerted only a minimal inhibitory effect. In eNOS-/- hearts the effect of CYP450 inhibitors on the BK response was significantly more pronounced than in WT hearts, indicating an enhanced contribution of CYP450 enzymes. These findings suggest that in isolated mouse hearts the BK-induced vasodilation is mediated by NO and CYP450 metabolites but not by prostaglandins. The CYP450 dependent vasodilator was was functionally up-regulated in eNOS-/- hearts and thus likely to compensate for the loss of eNOS in the coronary circulation.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Ding Z,Gödecke A,Schrader Jdoi
10.1038/sj.bjp.0704472subject
Has Abstractpub_date
2002-02-01 00:00:00pages
631-8issue
3eissn
0007-1188issn
1476-5381journal_volume
135pub_type
杂志文章abstract:BACKGROUND AND PURPOSE:Intestinal mucositis is a common side-effect of irinotecan-based cancer chemotherapy regimens. This mucositis is associated with cytokine activation and NO synthesis. Production of IL-18 is up-regulated in patients suffering from inflammatory bowel disease. Therefore, we have investigated the rol...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12584
更新日期:2014-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Imiquimod is an immunomodulator approved for the treatment of basal cell carcinoma and has adverse side effects, including taste disturbances. Paracrine transmission, representing cell-cell communication within taste buds, has the potential to shape the final signals that taste buds transmit to t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13567
更新日期:2016-11-01 00:00:00
abstract::The effects of the angiotensin-converting-enzyme inhibitor (ACEI) ramiprilat, the angiotensin II type 1 receptor antagonist (AT(1)A) candesartan, and the combination of both drugs on infarct size (IS) resulting from regional myocardial ischaemia were studied in pigs. Both ACEI and AT(1)A reduce myocardial IS by a brad...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703544
更新日期:2000-09-01 00:00:00
abstract::The neonate has an unusual capacity for survival and the possibility exists that mechanisms for controlling stress responses may differ in the developing animal. In adults both endogenous and exogenous opioids can modulate the corticosterone responses to stress. We have studied this effect in neonatal rats and found t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb08990.x
更新日期:1987-05-01 00:00:00
abstract::1. We investigated in the present study whether 5-HT is able to exert direct relaxant responses in canine basilar and middle cerebral arteries via the 5-HT7 receptor. 2. In arterial rings deprived of endothelium and pre-contracted with prostaglandin F2 alpha (2 microM), 5-HT, 5-carboxamidotryptamine (5-CT), 5-methoxyt...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702580
更新日期:1999-06-01 00:00:00
abstract::1. Recent studies have shown that sodium butyrate and other short-chain fatty acids (SCFAs) can prevent inflammation in colon diseases. Our aim was to elucidate whether sodium butyrate and SCFAs regulate the inflammatory responses in different neural inflammation models in cell cultures. 2. Inflammatory responses to L...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705682
更新日期:2004-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:We have previously shown that lipid mediators, produced by phospholipase D and C, are generated in OX(1) orexin receptor signalling with high potency, and presumably mediate some of the physiological responses to orexin. In this study, we investigated whether the ubiquitous phospholipase A(2) (PL...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00535.x
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Inhibitors of phosphodiesterase 5 (PDE5) affect signalling pathways by elevating cGMP, which is a second messenger involved in processes of neuroplasticity. In the present study, the effects of the PDE5 inhibitor, sildenafil, on the pathological features of Alzheimer's disease and on memory-relat...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01517.x
更新日期:2011-12-01 00:00:00
abstract::1. The aim of the present study was to investigate the role of nitric oxide (NO), histamine and leukotrienes in bronchial obstruction. For this, guinea-pigs immunised against ovalbumin were studied under anaesthesia during challenge with antigen or agonists. 2. Challenge with nebulised antigen (0.1-1 mg) elicited dose...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb15950.x
更新日期:1995-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Cannabis extracts and several cannabinoids have been shown to exert broad anti-inflammatory activities in experimental models of inflammatory CNS degenerative diseases. Clinical use of many cannabinoids is limited by their psychotropic effects. However, phytocannabinoids like cannabidiol (CBD), d...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01379.x
更新日期:2011-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Betulinic acid (BA) is a naturally occurring triterpenoid widely distributed throughout the plant kingdom. We previously reported that BA inhibits lipopolysaccharide (LPS)-induced interleukin-6 production through modulation of nuclear factor κB (NF-κB) in human peripheral blood mononuclear cells ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.01112.x
更新日期:2011-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Alogliptin, a highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor, enhances incretin action and pioglitazone enhances hepatic and peripheral insulin actions. Here, we have evaluated the effects of combining these agents in diabetic mice. EXPERIMENTAL APPROACH:Effects of short-term treatmen...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00145.x
更新日期:2009-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Thromboxane A(2) and endothelial dysfunction are implicated in the development of pulmonary hypertension. The receptor-transduction pathway for U46619 (9,11-dideoxy-9 alpha, 11 alpha-methanoepoxy prostaglandin F(2 alpha))-induced contraction was examined in endothelium-intact (E+) and denuded (E-...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2008.00084.x
更新日期:2009-06-01 00:00:00
abstract::We have recently shown that in polymorphonuclear leukocytes, 11-keto boswellic acids (KBAs) induce Ca2+ mobilisation and activation of mitogen-activated protein kinases (MAPK). Here we addressed the effects of BAs on central signalling pathways in human platelets and on various platelet functions. We found that beta-B...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706366
更新日期:2005-10-01 00:00:00
abstract::1 N-2-Chlorethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP 4) 50 mg/kg intraperitoneally, produced a long-term decrease in the capacity of brain homogenates to accumulate noradrenaline with significant effect 8 months after the injection. It had no effect on the noradrenaline uptake in homogenates from the striatu...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1976.tb08619.x
更新日期:1976-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Stress is believed to be associated with the development of neuropsychiatric disorders, including Alzheimer's disease (AD). We have studied mechanisms implicated in vulnerability to stress and the relationship with changes in AD-related markers. EXPERIMENTAL APPROACH:Anhedonia induced by a chron...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01602.x
更新日期:2012-02-01 00:00:00
abstract::YM471, (Z)-4'-[4,4-difluoro-5-[2-(4-dimethylaminopiperidino)-2-oxoethylidene]-2,3,4,5-tetrahydro-1H-1-benzoazepine-1-carbonyl]-2-phenylbenzanilide monohydrochloride, is a newly synthesized potent vasopressin (AVP) receptor antagonist. Its effects on binding to and signal transduction by cloned human AVP receptors (V(1...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704117
更新日期:2001-07-01 00:00:00
abstract::1. The action of substance P (SP) on the release of gamma-aminobutyric acid (GABA) and acetylcholine (ACh) and on contraction were studied in strips of the guinea-pig urinary bladder. Substance P induced a dose-dependent contraction of strips of guinea-pig urinary bladder (EC50 = 1.2 x 10(-9) M). This contraction was ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb12615.x
更新日期:1989-10-01 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:BACKGROUND AND PURPOSE:Pancreatitis represents a life-threatening inflammatory condition where leucocytes, cytokines and vascular endothelium contribute to the development of the inflammatory disease. The glucocorticoid-induced tumour necrosis factor (TNF) receptor family-related protein (GITR) is a costimulatory molec...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.01123.x
更新日期:2011-03-01 00:00:00
abstract::1. By use of a number of analogues of adenine nucleotides, the structure-activity relationships of the human platelet receptor for adenosine 5'-diphosphate (ADP) mediating increases in intracellular calcium were investigated, and compared with the known structure-activity relationships for induction by ADP of platelet...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb12869.x
更新日期:1993-03-01 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::The administration of arachidonic acid (AA) to the isolated perfused heart of the rat usually produced biphasic coronary responses characterized by initial vasoconstriction followed by prolonged vasodilatation. However, some responses were predominantly vasoconstrictor or vasodilator. The non-steroidal anti-inflammato...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb08783.x
更新日期:1982-02-01 00:00:00
abstract::Carbon monoxide (CO) is firmly established as an important, physiological signalling molecule as well as a potent toxin. Through its ability to bind metal-containing proteins, it is known to interfere with a number of intracellular signalling pathways, and such actions can account for its physiological and pathologica...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.12760
更新日期:2015-03-01 00:00:00
abstract::1. The uptake and release of (3)H-digitoxigenin by electrically driven, guinea-pig isolated atria (frequency 180/min) has been determined for two different medium concentrations of the genin. Both concentrations-1 x 10(-7) and 5 x 10(-7) g/ml.-caused a pronounced increase in contractile force.2. The uptake of (3)H-dig...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1968.tb08490.x
更新日期:1968-11-01 00:00:00
abstract::Psoriasis is a chronic inflammatory disease affecting 1-3% of the general population. Among psoriatic patients, 5-40% are affected by psoriatic arthritis. Due to the chronic nature of the disease, patients suffer from substantial psychological and financial burdens, thus adding to a significantly impaired quality of l...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1476-5381.2010.00702.x
更新日期:2010-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:There is increasing evidence that angiotensin II (Ang II) is associated with the occurrence of ventricular arrhythmias. However, little is known about the electrophysiological effects of Ang II on ventricular repolarization. The rapid component of the delayed rectifier K(+) current (I(Kr)) plays ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/bjp.2008.95
更新日期:2008-05-01 00:00:00
abstract::1 The effect of 5-hydroxytryptamine (5-HT) on acid secretion by a rat isolated stomach preparation has been studied. 2 5-HT at 10(-5)M in the serosal bathing fluid produced significant inhibition of the acid secretory responses to histamine, pentagastrin and isoprenaline but was without effect on basal secretion or th...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1983.tb09371.x
更新日期:1983-01-01 00:00:00
abstract::We have demonstrated previously that infusion of angiotensin II (AngII) into hyperlipidemic mice augments atherosclerosis and results in the formation of abdominal aortic aneurysms (AAA). The purpose of this study was to determine the role of aldosterone in these AngII-induced vascular pathologies. Male apolipoprotein...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706098
更新日期:2005-02-01 00:00:00
abstract::1. The central and peripheral effects of the omega (benzodiazepine) site ligands, clonazepam, alpidem, zolpidem, triazolam, flumazenil, ethyl beta carboline-3-carboxylate (beta-CCE) and N-methyl beta carboline-3-carboxylate (beta-CCM) on intestinal myoelectrical activity were evaluated in conscious rats, chronically f...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb16204.x
更新日期:1994-09-01 00:00:00