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 a critical role in cardiac repolarization. Hence, the aim of this study was to assess the effect of Ang II on I(Kr) in guinea-pig ventricular myocytes. EXPERIMENTAL APPROACH:The whole-cell patch-clamp technique was used to record I(Kr) in native cardiocytes and in human embryonic kidney (HEK) 293 cells, co-transfected with human ether-a-go-go-related gene (hERG) encoding the alpha-subunit of I(Kr) and the human Ang II type 1 (AT(1)) receptor gene. KEY RESULTS:Ang II decreased the amplitude of I(Kr) in a concentration-dependent manner with an IC(50) of 8.9 nM. Action potential durations at 50% (APD(50)) and 90% (APD(90)) repolarization were prolonged 20% and 16%, respectively by Ang II (100 nM). Ang II-induced inhibition of the I(Kr) was abolished by the AT(1) receptor blocker, losartan (1 muM). Ang II decreased hERG current in HEK293 cells and significantly delayed channel activation, deactivation and recovery from inactivation. Moreover, PKC inhibitors, stausporine and Bis-1, significantly attenuated Ang II-induced inhibition of I(Kr). CONCLUSIONS AND IMPLICATIONS:Ang II produces an inhibitory effect on I(Kr)/hERG currents via AT(1) receptors linked to the PKC pathway in ventricular myocytes. This is a potential mechanism by which elevated levels of Ang II are involved in the occurrence of arrhythmias in cardiac hypertrophy and failure.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Wang YH,Shi CX,Dong F,Sheng JW,Xu YFdoi
10.1038/bjp.2008.95subject
Has Abstractpub_date
2008-05-01 00:00:00pages
429-39issue
2eissn
0007-1188issn
1476-5381pii
bjp200895journal_volume
154pub_type
杂志文章abstract：:1 The effects of a subconstrictor dose of histamine (9 x 10(-7) mol/l) on the responses of the isolated perfused ear artery of the rabbit to electrical stimulation (E.S.) and to exogenous noradrenaline (NA) were investigated.2 Both intraluminal (I/L) and extraluminal (E/L) histamine potentiated responses to E.S. and t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1979.tb08684.x
更新日期：1979-11-01 00:00:00
abstract：:1. Hypercholesterolaemia often occurs in patients with type 2 diabetes, who therefore encounter administration of HMG-CoA reductase inhibitors. Alteration of pancreatic beta-cell function leading to an impaired insulin secretory response to glucose plays a crucial role in the pathogenesis of type 2 diabetes. Therefore...
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1981.tb09131.x
更新日期：1981-02-01 00:00:00
abstract：:G protein-coupled receptors are one of the most actively studied families of proteins. However, despite the ubiquity of protein dimerization and oligomerization as a structural and functional motif in biology, until the last decade they were generally considered as monomeric, non-interacting polypeptides. For the meta...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1038/sj.bjp.0707490
更新日期：2008-03-01 00:00:00
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journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1995.tb15960.x
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1985.tb11078.x
更新日期：1985-08-01 00:00:00
abstract：:1. Insulin antibodies were induced in young guinea-pigs of both sexes weighing 300-400 g and housed in a room maintained at 28 degrees C+/-2 degrees C, by subcutaneous injection of 2 ml of freshly prepared insulin antigen emulsion between the shoulders once every month.2. To estimate the titre of serum antibody the se...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1971.tb07087.x
更新日期：1971-05-01 00:00:00
abstract：:1. The 37 amino acid human calcitonin gene-related peptide (CGRP), was injected intra-arterially into the isolated, blood perfused spleen of the dog. 2. The only vascular response observed to CGRP, once threshold had been reached (10-20 fmol), was a dose-dependent splenic arterial vasodilatation. 3. The mean intra-art...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb11890.x
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journal_title：British journal of pharmacology
pub_type： 评论,杂志文章,评审
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.15209
更新日期：2020-07-22 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb12092.x
更新日期：1990-09-01 00:00:00
abstract：:1. Whole-cell patch-clamp recordings were made from smooth muscle cells isolated from the longitudinal muscle layer of guinea-pig ileum. Carbachol (acting at muscarinic receptors) or histamine (acting at H1 histamine receptors) suppressed Ca2+ channel current. The effect of either agonist had an initial transient comp...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702112
更新日期：1998-10-01 00:00:00
abstract：:In this study, the mechanism of nicotine-induced hippocampal acetylcholine (ACh) release in awake, freely moving rats was examined using in vivo microdialysis. Systemic administration of nicotine (0.4 mg kg(-1), s.c.) increased the levels of ACh in hippocampal dialysates. The nicotine-induced hippocampal ACh release w...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702683
更新日期：1999-07-01 00:00:00
abstract：:1. Diabetes mellitus produces marked abnormalities in motor nerve conduction, but the mechanism is not clear. In the present study we hypothesized that in the streptozotocin (STZ)-induced diabetic rat impaired vasodilator function is associated with reduced endoneural blood flow (EBF) which may contribute to nerve dys...
journal_title：British journal of pharmacology
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doi：10.1038/sj.bjp.0702856
更新日期：1999-10-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701955
更新日期：1998-07-01 00:00:00
abstract：:1. The macroscopic currents induced in cultured rat melanotrophs by exogenous gamma-aminobutyric acid (GABA) were analysed using the patch clamp recording technique. 2. Using various concentrations of intra- and extracellular chloride it was demonstrated that the conductance activated by GABA was chloride selective. S...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb11359.x
更新日期：1987-11-01 00:00:00
abstract：:The effects of repeated electroconvulsive shock (ECS) administration, repeated desmethylimipramine injection (5 mg kg-1, twice daily for 14 days) and acute administration of the beta-adrenoceptor, clenbuterol, on 5-hydroxytryptamine (5-HT)- and dopamine-mediated behaviours in mice have been examined. All three treatme...
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doi：10.1111/j.1476-5381.1983.tb10044.x
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abstract：:Hydrogen sulfide (H(2)S) is described as a mediator of diverse biological effects, and is known to produce irritation and injury in the lung following inhalation. Recently, H(2)S has been found to cause contraction in the rat urinary bladder via a neurogenic mechanism. Here, we studied whether sodium hydrogen sulfide ...
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更新日期：1994-09-01 00:00:00
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pub_type： 杂志文章
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journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1995.tb13297.x
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1979.tb08691.x
更新日期：1979-11-01 00:00:00
abstract：:1. The distribution and some pharmacological properties of centrally located dextromethorphan high-affinity binding sites were investigated by in vitro autoradiography. 2. Sodium chloride (50 mM) induced a 7 to 12 fold increase in dextromethorphan binding to rat brain in all areas tested. The effect of sodium was conc...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701043
更新日期：1997-04-01 00:00:00
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journal_title：British journal of pharmacology
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journal_title：British journal of pharmacology
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更新日期：2013-03-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701151
更新日期：1997-06-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
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更新日期：2019-07-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13124
更新日期：2015-07-01 00:00:00
abstract：:The incubation of rat peritoneal macrophages in the presence of staurosporine, a non-specific protein kinase inhibitor, induced interleukin-6 (IL-6) production in a time- and concentration-dependent manner at 6.3-63 nM, but at 210 nM, the stimulant effect on IL-6 production was reduced. The levels of IL-6 mRNA as dete...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702659
更新日期：1999-07-01 00:00:00
