Document Detail

Role of K+ ATP channels and adenosine in the regulation of coronary blood flow during exercise with normal and restricted coronary blood flow.
MedLine Citation:
PMID:  8613554     Owner:  NLM     Status:  MEDLINE    
Regulation of coronary vasomotor tone during exercise is incompletely understood. We investigated the contributions of K+ ATP channels and adenosine to the coronary vasodilation that occurs during exercise in the normal heart and in the presence of a coronary artery stenosis. Dogs that were chronically instrumented with a Doppler flow probe, hydraulic occluder, and indwelling catheter on the left anterior descending coronary artery were exercised on a treadmill to produce heart rates of approximately 200 beats/min. By graded inflation of the occluder to produce a wide range of coronary stenosis severities, we determined the coronary pressure-flow relation. K+ atp channel blockade with intracoronary glibenclamide (10-50 microgram/kg per min) decreased coronary blood flow during exercise at coronary pressures within and below the autoregulatory range, indicating that coronary K+ ATP channel activation is critical for producing coronary vasodilation with either normal arterial inflow or when flow is restricted by a coronary artery stenosis. Adenosine receptor blockade with intravenous 8-phenyltheophylline (5 mg/kg) had no effect on coronary flow at pressures within the autoregulatory range but decreased flow at pressures < 55 mmHg. In contrast, in the presence of K+ ATP channel blockade, the addition of adenosine receptor blockade further decreased coronary flow even at coronary pressures in the autoregulatory range, indicating increased importance of the vasodilator influence of endogenous adenosine during exercise when K+ atp channels are blocked. Intracoronary adenosine (50 microgram/kg per min) increased coronary flow at perfusion pressures both within and below the autoregulatory range. In contrast, selective K+ ATP channel activation with intracoronary pinacidil (0.2-5.0 microgram/kg per min) increased flow at normal but not at lower coronary pressures (< 55 mmHg). This finding demonstrates that not all K+ ATP channels are activated during exercise at pressures in the autoregulatory range, but that most K+ ATP channels are recruited as pressures approach the lower end of the autoregulatory plateau. Thus, K+ ATP channels and endogenous adenosine play a synergistic role in maintaining vasodilation during exercise in normal hearts and distal to a coronary artery stenosis that results in myocardial hypoperfusion during exercise.
D J Duncker; N S van Zon; Y Ishibashi; R J Bache
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  97     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1996 Feb 
Date Detail:
Created Date:  1996-06-05     Completed Date:  1996-06-05     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  996-1009     Citation Subset:  AIM; IM    
Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
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MeSH Terms
Adenosine / physiology*
Coronary Circulation / drug effects*
Glyburide / pharmacology
Guanidines / administration & dosage
Hemodynamics / drug effects
Myocardial Contraction / drug effects
Physical Exertion*
Potassium Channel Blockers
Potassium Channels / physiology*
Receptors, Purinergic P1 / antagonists & inhibitors
Theophylline / analogs & derivatives,  pharmacology
Vasodilator Agents / pharmacology
Grant Support
Reg. No./Substance:
0/Guanidines; 0/Potassium Channel Blockers; 0/Potassium Channels; 0/Receptors, Purinergic P1; 0/Vasodilator Agents; 10238-21-8/Glyburide; 58-55-9/Theophylline; 58-61-7/Adenosine; 85371-64-8/Pinacidil; 961-45-5/8-phenyltheophylline

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