Vasodilatory effect of nicorandil on coronary arterial microvessels: its dependency on vessel size and the involvement of the ATP-sensitive potassium channels.
We aimed to clarify the size dependency of nicorandil-induced dilation in coronary microcirculation and the involvement of adenosine triphosphate (ATP)-sensitive potassium channels. Coronary arterial microvessels were observed through a microscope equipped with a floating objective in anesthetized open-chest dogs (n = 29). Heart rate and mean aortic pressure were maintained at control level. In 16 dogs, nicorandil was infused into the coronary in a cumulative fashion (0.1, 1.0, 10, and 100 micrograms/kg/min, for 5 min for each dose). In 13 dogs, glibenclamide (10 microM) was topically applied onto the observed area, and nicorandil was similarly infused. Nicorandil dilated vessels < 100 microns in diameter at all applied doses in a dose-dependent manner. Glibenclamide abolished the dilation of these vessels at the lower two doses. Vessels > 100 microns in diameter dilated only at the two higher doses and the dilation was not affected by glibenclamide. These data suggest that the vessels < 100 microns are more sensitive to this agent than other size vessels, and that ATP-sensitive potassium channels are involved in the nicorandil-induced dilation of vessels smaller than 100 microns, whereas the dilation of other size vessels occurs independently of this channel.
Akai
K
K
First Department of Internal Medicine, Tohoku University, School of Medicine, Sendai, Japan.
Wang
Y
Y
Sato
K
K
Sekiguchi
N
N
Sugimura
A
A
Kumagai
T
T
Komaru
T
T
Kanatsuka
H
H
Shirato
K
K
D000255:Adenosine Triphosphate; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000648:ultrastructure; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007261:Infusions, Intra-Arterial; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D015221:Potassium Channels / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil; D000255:Adenosine Triphosphate; D005905:Glyburide