Involvement of ATP-sensitive K+ channels in the sustained coronary vasodilator response to adenosine in dogs.
Coronary vasodilator mechanisms of adenosine were investigated in isolated canine papillary muscle preparations cross-circulated through the anterior septal artery with support dogs. Infusions of adenosine (1-3000 nmol/min) for 3 min into this artery caused a transient increase (the initial phase) in blood flow followed by a sustained increase (the sustained phase), and single-bolus intra-arterial injections of adenosine (0.3-1000 nmol) produced only a transient increase in blood flow. The force of contraction of the papillary muscle was virtually unaffected. The increase in blood flow in the sustained phase was antagonized by glibenclamide (6 mumol/kg i.v.), a blocker of ATP-sensitive K+ channels, administered to support dogs whereas increases in both phases were antagonized by 8-phenyltheophylline (12 mumol/kg i.v.), a non-selective adenosine receptor antagonist, administered in a similar way. The transient increase in blood flow caused by single-bolus injections of adenosine was reduced in duration rather than in peak value by glibenclamide. Thus, it appears that opening of ATP-sensitive K+ channels gradually becomes involved in the vasodilator mechanisms for adenosine A2 receptor-mediated, sustained vasodilation.
Orito
K
K
Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
Satoh
K
K
Taira
N
N
D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D007269:Injections, Intra-Arterial; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine; D005905:Glyburide