Glibenclamide-induced oscillation of canine coronary artery is independent of myocardial ischemia.
To investigate the in vivo role of the ATP-sensitive potassium channel (KATP) in the coronary arteries, we examined the effects of intravenous (i.v.) glibenclamide (GLB, 0.3, 1.0, and 3.0 mg/kg), a specific KATP blocker, in chronically instrumented dogs. Epicardial coronary artery diameter (CoD) and coronary blood flow (CBF) were measured continuously. CoD and CBF oscillated in all 6 dogs after injection of 3 mg/kg GLB. CoD oscillated only slightly, with a decrease of 2.3 +/- 0.4%; CBF showed marked oscillation, with a peak flow rate of 21.9 +/- 2.7 ml/min (+26.6%) and a trough flow rate of 10.3 +/- 2.9 ml/min (-46.3%) (baseline flow rate was 17.8 +/- 2.4 ml/min). GLB 1 mg/kg produced a slight decrease in CBF without oscillation, and at 0.3 mg/kg had almost no effect. These oscillations were not associated with a decrease in myocardial blood flow as measured by the hydrogen gas clerance method. Nicorandil (0.2 mg/kg), cromakalim (20 micrograms/kg), and diltiazem (0.2 mg/kg) almost completely suppressed the GLB-induced oscillations, but nitroglycerin (NTG 15 micrograms/kg) did not. Thus, oscillation of large and small coronary arteries was induced by GLB and was independent of myocardial ischemia. In addition, these findings suggest that KATP has an important in vivo role in modulating large and small coronary artery tone through activation of the voltage-dependent Ca2+ channel.
Nakae
I
I
First Department of Internal Medicine, Shiga University of Medical Science, Seta, Japan.
Quan
L
L
Sugimoto
Y
Y
Tsutamoto
T
T
Kinoshita
M
M
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000033:anatomy & histology / Q000187:drug effects* / Q000503:physiopathology*; D019806:Cromakalim; D004110:Diltiazem / Q000494:pharmacology; D004285:Dogs; D005260:Female; D005905:Glyburide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D020108:Nicorandil; D019335:Nitroarginine; D005996:Nitroglycerin / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D019335:Nitroarginine; D009536:Niacinamide; D020108:Nicorandil; D000255:Adenosine Triphosphate; D001120:Arginine; D004110:Diltiazem; D005996:Nitroglycerin; D005905:Glyburide