| Anti-arrhythmic and electrophysiological effects of the endothelin receptor antagonists, BQ-123 and PD161721. | |
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MedLine Citation:
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PMID: 11734190 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The effects of the endothelin ET(A), (BQ-123) and endothelin ET(A/B) (PD161721) receptor antagonists were investigated on ischaemia-induced arrhythmias and on the maximum following frequency. The study was carried out in Langendorff perfused rat hearts subjected to coronary artery occlusion in which the severity of arrhythmias, coronary perfusion pressure and heart rate were measured. The % incidence of ischaemia-induced irreversible ventricular fibrillation (ventricular fibrillation) was reduced significantly from 58%, in control rat hearts, to 0% (at 10(-7) and 10(-6) M PD161721 and 10(-6) M BQ-123 P<0.05). Maximum following frequency was measured in guinea-pig isolated atria. In the presence of normal extracellular [K(+)], BQ-123 and PD161721, at 10(-6) M, significantly decreased the maximum following frequency from 9.0+/-0.7 to 7.2+/-0.4 and from 8.3+/-0.4 to 6.7+/-0.3 Hz, respectively (P<0.05). These effects were not potentiated by raising the extracellular [K(+)] with the exception of 10(-9) M PD161721. In contrast, lignocaine's ability to reduce the maximum following frequency was greater in elevated (e.g. at 1.7x10(-4) M from 8.4+/-0.3 to 2.5+/-0.6 Hz) than in normal [K(+)] (from 9.0+/-0.3 to 4.9+/-0.5 Hz). In conclusion, both BQ-123 and PD161721 had an anti-fibrillatory effect in isolated rat hearts that may be due, at least in part, to an ability to reduce the maximum following frequency. This latter effect is unlikely to be due to Na(+) channel blockade since it was not markedly potentiated by elevation of extracellular [K(+)]. |
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Authors:
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T R Crockett; G A Scott; N W McGowan; K A Kane; C L Wainwright |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of pharmacology Volume: 432 ISSN: 0014-2999 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2001 Nov |
Date Detail:
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Created Date: 2001-12-05 Completed Date: 2002-02-11 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 71-7 Citation Subset: IM |
Affiliation:
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Department of Physiology and Pharmacology, University of Strathclyde, Strathclyde Institute for Biomedical Sciences, 27 Taylor Street, G4 0NR, Scotland, Glasgow, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-Arrhythmia Agents / pharmacology* Arrhythmias, Cardiac / etiology, physiopathology, prevention & control Atrial Function Dioxins / pharmacology* Dose-Response Relationship, Drug Electrophysiology Guinea Pigs Heart / drug effects, physiology Heart Atria / drug effects Heart Rate / drug effects Lidocaine / pharmacology Male Muscle Contraction / drug effects Myocardial Ischemia / complications Peptides, Cyclic / pharmacology* Perfusion Pressure Rats Rats, Sprague-Dawley Receptors, Endothelin / antagonists & inhibitors* |
| Chemical | |
Reg. No./Substance:
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0/Anti-Arrhythmia Agents; 0/Dioxins; 0/PD 161721; 0/Peptides, Cyclic; 0/Receptors, Endothelin; 136553-81-6/cyclo(Trp-Asp-Pro-Val-Leu); 137-58-6/Lidocaine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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