Document Detail


Effect of K+ATP channel and adenosine receptor blockade during rest and exercise in congestive heart failure.
MedLine Citation:
PMID:  17478726     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
K(+)(ATP) channels are important metabolic regulators of coronary blood flow (CBF) that are activated in the setting of reduced levels of ATP or perfusion pressure. In the normal heart, blockade of K(+)(ATP) channels results in a approximately 20% reduction in resting CBF but does not impair the increase in CBF that occurs during exercise. In contrast, adenosine receptor blockade fails to alter CBF or myocardial oxygen consumption (MVO(2)) in the normal heart but contributes to the increase in CBF during exercise when vascular K(+)(ATP) channels are blocked. Congestive heart failure (CHF) is associated with a decrease in CBF that is matched to a decrease in MVO(2) suggesting downregulation of myocardial energy utilization. Because myocardial ATP levels and coronary perfusion pressure are reduced in CHF, this study was undertaken to examine the role of K(+)(ATP) channels and adenosine in dogs with pacing-induced CHF. Myocardial blood flow (MBF) and MVO(2) were measured during rest and treadmill exercise before and after K(+)(ATP) channel blockade with glibenclamide (50 microg/kg/min ic) or adenosine receptor blockade with 8-phenyltheophylline (8-PT; 5 mg/kg iv). Inhibition of K(+)(ATP) channels resulted in a decrease in CBF and MVO(2) at rest and during exercise without a change in the relationship between CBF and MVO(2). In contrast, adenosine receptor blockade caused a significant increase in CBF that occurred secondary to an increase of MVO(2). These findings demonstrate that coronary K(+)(ATP) channel activity contribute to the regulation of resting MBF in CHF, and that endogenous adenosine may act to inhibit MVO(2) in the failing heart.
Authors:
Jay H Traverse; YingJie Chen; MingXiao Hou; Yunfang Li; Robert J Bache
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-05-03
Journal Detail:
Title:  Circulation research     Volume:  100     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-06-08     Completed Date:  2007-06-19     Revised Date:  2011-04-20    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1643-9     Citation Subset:  IM    
Affiliation:
Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA. trave004@umn.edu
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Animals
Anti-Arrhythmia Agents / pharmacology
Blood Flow Velocity / drug effects
Cardiac Pacing, Artificial
Coronary Circulation / drug effects
Disease Models, Animal
Dogs
Exercise Test
Glyburide / pharmacology
Heart / drug effects,  physiopathology*
Heart Failure / physiopathology*
Oxygen Consumption / drug effects
Physical Exertion* / drug effects
Pinacidil / pharmacology
Potassium Channel Blockers / pharmacology*
Potassium Channels / drug effects*,  metabolism
Purinergic P1 Receptor Antagonists*
Rest
Theophylline / analogs & derivatives,  pharmacology
Vasodilator Agents / pharmacology
Grant Support
ID/Acronym/Agency:
HL20598/HL/NHLBI NIH HHS; HL21872/HL/NHLBI NIH HHS; HL71790/HL/NHLBI NIH HHS; R01 HL071790-01A1/HL/NHLBI NIH HHS; R01 HL071790-02/HL/NHLBI NIH HHS; R01 HL071790-03/HL/NHLBI NIH HHS; R01 HL071790-04/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/Potassium Channel Blockers; 0/Potassium Channels; 0/Purinergic P1 Receptor Antagonists; 0/Vasodilator Agents; 10238-21-8/Glyburide; 56-65-5/Adenosine Triphosphate; 58-55-9/Theophylline; 85371-64-8/Pinacidil; 961-45-5/8-phenyltheophylline

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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