| Calcitonin gene-related peptide receptor antagonism does not affect the severity of myocardial ischemia during atrial pacing in dogs with coronary artery stenosis. | |
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MedLine Citation:
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PMID: 18997059 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Calcitonin gene-related peptide (CGRP) is a sensory neuropeptide that also has potent vasodilator activity. There are conflicting preclinical reports regarding the effect of CGRP receptor antagonism in the setting of myocardial ischemia. The present study was conducted in a canine model in which regional myocardial ischemia was reproducibly evoked by serial periods of atrial pacing (80 beats per min above baseline rate) in the presence of a 40% stenosis of the left anterior descending (LAD) coronary artery. Ischemia severity was quantitated by changes in unipolar epicardial electrograms (EG) recorded in the area of ischemia. In validation studies, the calcium entry blocker diltiazem reduced ischemia severity (before versus after treatment: DeltaEG, 1.92 +/- 0.23 versus 0.54 +/- 0.24 mV; p < 0.05) and tended to increase LAD flow (7.7 +/- 0.7 versus 9.4 +/- 1.4 ml/min; p = 0.10), whereas the coronary constrictor serotonin increased ischemia severity (before versus after treatment: DeltaEG, 2.11 +/- 0.44 versus 4.90 +/- 1.46 mV; p < 0.05) concomitant with a reduction in LAD flow (9.1 +/- 1.1 versus 5.4 +/- 1.5 ml/min; p < 0.05). A 30 microg/kg/min i.v. infusion test dose of the CGRP receptor antagonist CGRP((8-37)) was validated by demonstrating complete block of the depressor effects of exogenous i.v. 0.03 to 0.3 microg/kg CGRP. This dose of CGRP((8-37)), administered either intravenously or intra-atrially, had no effect on ischemia severity or paced LAD flow, indicating no intrinsic effect of CGRP receptor antagonism on the severity of acute myocardial ischemia. Likewise, the administration of a hemodynamically active dosing regimen of CGRP (0.03 microg/kg/min i.v.) had no effect on paced coronary flow or ischemia severity, suggesting no major role of CGRP in regulating ischemic blood flow. |
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Authors:
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Christopher P Regan; Gary L Stump; Stefanie A Kane; Joseph J Lynch |
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Publication Detail:
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Type: Journal Article Date: 2008-11-07 |
Journal Detail:
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Title: The Journal of pharmacology and experimental therapeutics Volume: 328 ISSN: 1521-0103 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 2009 Feb |
Date Detail:
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Created Date: 2009-01-23 Completed Date: 2009-02-23 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: United States |
Other Details:
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Languages: eng Pagination: 571-8 Citation Subset: IM |
Affiliation:
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Department of Integrative Systems Neuroscience, Merck Research Laboratories, West Point, PA 19486, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calcitonin Gene-Related Peptide / therapeutic use* Cardiac Pacing, Artificial* Coronary Circulation / physiology Coronary Stenosis / complications*, physiopathology Coronary Vessels / drug effects*, physiology Diltiazem / therapeutic use Disease Models, Animal Dogs Female Heart Atria / drug effects, physiopathology Hemodynamics / drug effects Male Myocardial Ischemia / etiology, therapy* Receptors, Calcitonin Gene-Related Peptide / antagonists & inhibitors* Serotonin / therapeutic use |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Calcitonin Gene-Related Peptide; 42399-41-7/Diltiazem; 50-67-9/Serotonin; 83652-28-2/Calcitonin Gene-Related Peptide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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