Abstract:
:1. The effect of basal tension (transmural tensions 235 +/- 29 mg wt (low tension: equivalent to approximately 16 mmHg) and 305 +/- 34 mg wt (high tension: equivalent to 35 mmHg)) on rat pulmonary resistance artery responses to endothelin-1 (ET-1) and the selective ET(B)-receptor agonist sarafotoxin S6c (S6c) were studied. The effects of nitric oxide synthase inhibition with N(omega)-nitro-L-arginine methylester (L-NAME, 100 microM) on ET receptor-induced responses, as well as vasodilator responses to acetylcholine (ACh) and S6c, were also investigated. Changes with development of pulmonary hypertension, induced by two weeks of chronic hypoxia, were determined. 2. Control rat preparations showed greatest sensitivity for ET-1 when put under low tension (pEC50: 8.1 +/- 0.1) compared with at the higher tension (pEC50: 7.7 +/- 0.1) and there were significant increases in maximum contractile responses to S6c (approximately 80%) and noradrenaline (approximately 60%) when put under high tension. 3. In control pulmonary resistance arteries, both ET-1 and S6c produced potent vasoconstrictor responses. S6c was 12 fold more potent than ET-1 in vessels set at low tension (S6c pEC50: 9.2 +/- 0.1) and 200 fold more potent than ET-1 when the vessels were set at high tension (S6c pEC50: 9.0 +/- 0.1). Chronic hypoxia did not change the potencies of ET-1 and S6c but did significantly increase the maximum contractile response to ET-1 by 60% (at low tension) and 130% (at high tension). 4. In control rat vessels, L-NAME itself caused small increases in vascular tone (5-8 mg wt tension) in 33-56% of vessels. In the chronic hypoxic rats, in vessels set at high tension, L-NAME-induced tone was evident in 88% of vessels and had increased to 26.9 +/- 6.6 mg wt tension. Vasodilatation to sodium nitroprusside, in non-preconstricted vessels, was small in control rat vessels (2-6 mg wt tension) but increased significantly to 22.5 +/- 8.0 mg wt tension in chronic hypoxic vessels set at the higher tensions. Together, these results indicate an increase in endogenous tone in the vessels from the chronic hypoxic rats which is normally attenuated by nitric oxide production. 5. L-NAME increased the sensitivity to S6c 10 fold (low tension) and 6 fold (high tension) only in chronic hypoxic rat pulmonary resistance arteries. It had no effect on responses to ET-1 in any vessel studied. 6. Vasodilatation of pre-contracted vessels by ACh was markedly greater in the pulmonary resistance arteries from the chronic hypoxic rats (pIC50: 7.12 +/- 0.19, maximum: 72.1 +/- 0.2.0%) compared to their age-matched controls (pIC50: 5.77 +/- 0.15, maximum: 28.2 +/- 2.0%). There was also a 2.5 fold increase in maximum vasodilatation induced by ACh. 7. These results demonstrate that control rat preparations showed greatest sensitivity for ET-1 when set at the lower tension, equivalent to the pressure expected in vivo (approximately 16 mmHg). Pulmonary hypertension due to chronic hypoxia potentiated the maximum response to ET-1. Pulmonary resistance arteries from control animals exhibited little endogenous tone, but exposure to chronic hypoxia increased endogenous inherent tone which is normally attenuated by nitric oxide. Endogenous nitric oxide production may increase in pulmonary resistance arteries from chronic hypoxic rats and attenuate contractile responses to ET(B2) receptor stimulation. Relaxation to ACh was increased in pulmonary resistance arteries from chronic hypoxic rats.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
MacLean MR,McCulloch KMdoi
10.1038/sj.bjp.0701682subject
Has Abstractpub_date
1998-03-01 00:00:00pages
991-9issue
5eissn
0007-1188issn
1476-5381journal_volume
123pub_type
杂志文章abstract::1. The effects of paracetamol and lysine acetylsalicylate (L-AS) on high-threshold mechanonociceptors have been investigated by recording neural activity from the inflamed ankle joint in anaesthetized rats with mild adjuvant-induced monoarthritis. 2. Paracetamol (50 mg kg-1, i.v.) and L-AS (100 mg kg-1, i.v., equivale...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12404.x
更新日期:1991-09-01 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::1. Studies in rats suggest that PACAP modulates gastric acid secretion through the release of both histamine and somatostatin. 2. We characterized the effects of exogenous PACAP on gastric acid secretion in urethane-anesthetized mice implanted with a gastric cannula and in conscious 2-h pylorus ligated mice, and deter...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705739
更新日期:2004-05-01 00:00:00
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
更新日期:2011-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:mTOR inhibitors are currently used as immunosuppressants in transplanted patients and as promising anti-cancer agents. However, new-onset diabetes is a frequent complication occurring in patients treated with mTOR inhibitors such as rapamycin (Sirolimus). Here, we investigated the mechanisms asso...
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01716.x
更新日期:2012-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Tolerance induced by morphine and other opiates remains a major unresolved problem in the clinical management of pain. There is now good evidence for the importance of MAPKs in morphine-induced antinociceptive tolerance. A member of the MAPK kinase kinase family, TGF-β activated kinase 1 (TAK1) i...
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更新日期:2015-06-01 00:00:00
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doi:10.1038/sj.bjp.0707219
更新日期:2007-05-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb17261.x
更新日期:1973-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Chronic stress impairs GABAA (GABA type A) receptor-mediated inhibition in the hypothalamic paraventricular nucleus (PVN). It is not clear whether GABAB receptor function is also altered. We hypothesize that chronic stress alters GABAB receptor function in PVN corticotrophin-releasing hormone (CR...
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更新日期:2019-09-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704872
更新日期:2002-10-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706714
更新日期:2006-05-01 00:00:00
abstract::1 A rat isolated gastric mucosal preparation was used to monitor histamine output and acid secretion during stimulation by different secretagogues. 2 In non-stimulated preparations, spontaneous histamine output decreased over 450 min. 3 Stimulation of secretion with 4 (5)-methylhistamine or dibutyryl cyclic adenosine ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb09190.x
更新日期:1982-05-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb10177.x
更新日期:1986-01-01 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.tb15065.x
更新日期:1995-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Metformin, a small molecule, antihyperglycaemic agent, is a well-known activator of AMP-activated protein kinase (AMPK) and protects against cardiac fibrosis. However, the underlying mechanisms remain elusive. TGFβ1 is a key cytokine mediating cardiac fibrosis. Here, we investigated the effects o...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:2018-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0706688
更新日期:2006-04-01 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.tb11438.x
更新日期:1988-02-01 00:00:00
abstract::The study investigated the role of endothelin (ET) and the ET receptor subtypes ET(A) and ET(B) in mediating longitudinal contraction in the mouse proximal and distal colon. Cumulative concentration-response curves to a range of ET agonists (ET-1, ET-2, ET-3, (Ala(1,3,11,13)) ET and IRL 1620) were established by admin...
journal_title:British journal of pharmacology
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更新日期:2006-03-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1972.tb06865.x
更新日期:1972-10-01 00:00:00
abstract::1. Intraplantar administration of the nitric oxide (NO) donor, sodium nitroprusside (SNP), induces hyperaemia in the rat paw skin, which is in part due to release of calcitonin gene-related peptide (CGRP) from afferent nerve fibres. The present study examined whether prostaglandins or other inflammatory mediators part...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:1995-11-01 00:00:00
abstract::1. Contraction of the rabbit isolated saphenous vein is mediated by a heterogeneous endothelin (ET) receptor population. This study has characterized these receptor subtypes by use of several pharmacologically distinct ET receptor agonists and antagonists. 2. ET-1, ET-3, sarafotoxin S6c (STXc) and [Ala3,11]ET-1 produc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb14936.x
更新日期:1995-04-01 00:00:00
abstract::The physiological regulation of the immune system encompasses comprehensive anti-inflammatory mechanisms that can be harnessed for the treatment of infectious and inflammatory disorders. Recent studies indicate that the vagal nerve, involved in control of heart rate, hormone secretion and gastrointestinal motility, is...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0707264
更新日期:2007-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Resurgence in the use of chloroquine as a potential treatment for COVID-19 has seen recent cases of fatal toxicity due to unintentional overdoses. Protocols for the management of poisoning recommend diazepam, although there are uncertainties in its pharmacology and efficacy in this context. The a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.15101
更新日期:2020-11-01 00:00:00
abstract::1. We have characterized the 5-hydroxytryptamine (5-HT)-induced calcium signalling in endothelial cells from the human pulmonary artery. Using RT-PCR we show, that of all cloned G-protein coupled 5-HT receptors, these cells express only 5-HT1D beta, 5-HT2B and little 5-HT4 receptor mRNA. 2. In endothelial cells 5-HT i...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb16700.x
更新日期:1996-03-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:
更新日期:1971-10-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 临床试验,杂志文章
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更新日期:1970-05-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14574
更新日期:2020-02-01 00:00:00
abstract::1. Electrically-evoked contractions in different regions of the rabbit isolated pulmonary artery have been investigated using stimulation parameters generally assumed to stimulate nerves selectively. 2. In extrapulmonary artery, trains of stimuli (10 Hz; pulse width 0.1 ms) evoked monophasic contractions. In contrast,...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704863
更新日期:2002-10-01 00:00:00
abstract::1. The inhibitory effect of caffeine on the calcium channel current was investigated in cultured myometrial cells isolated from pregnant rats. 2. Caffeine inhibited the calcium channel current elicited from a holding potential of -70 mV in a concentration-dependent manner. The IC50 was estimated to be 35 mM. 3. The ca...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb12622.x
更新日期:1989-10-01 00:00:00