title: Effect of K+ATP channel and adenosine receptor blockade during rest and exercise in congestive heart failure.
abstract: 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.affiliation: Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA. trave004@umn.edu
authors.forename: Jay H
authors.initials: JH
authors.lastname: Traverse
authors.forename: YingJie
authors.initials: Y
authors.lastname: Chen
authors.forename: MingXiao
authors.initials: M
authors.lastname: Hou
authors.forename: Yunfang
authors.initials: Y
authors.lastname: Li
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Bache
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D005080:Exercise Test; D005905:Glyburide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006333:Heart Failure / Q000503:physiopathology*; D010101:Oxygen Consumption / Q000187:drug effects; D005082:Physical Exertion / Q000187:drug effects; D020110:Pinacidil / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D058915:Purinergic P1 Receptor Antagonists; D012146:Rest; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000889:Anti-Arrhythmia Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D058915:Purinergic P1 Receptor Antagonists; D014665:Vasodilator Agents; D020110:Pinacidil; D000255:Adenosine Triphosphate; D013806:Theophylline; C028322:8-phenyltheophylline; D005905:Glyburide