Cardiovascular effects of YM099, a novel K+ channel opener, in anesthetized and conscious dogs.
Cardiovascular effects of a newly synthesized benzoxadiazol derivative K+ channel opener, YM099, 2-(7,8-dihydro-6,6-dimethyl-6H-[1,4]oxazino[2,3- f][2,1,3]benzoxadiazol-8-yl) pyridine N-oxide, were evaluated in dogs. In pentobarbital-anesthetized dogs, YM099 (1-10 micrograms/kg i.v.), similarly to levcromakalim (1-10 micrograms/kg i.v.), dose dependently increased coronary artery blood flow, max.d p/dt and cardiac output, and decreased total peripheral resistance and mean blood pressure, with a small increase in heart rate. These vasodilator effects were antagonized by glibenclamide (3 mg/kg i.v.). Interestingly, YM099 selectively increased coronary artery blood flow, although it increased carotid, coronary, mesenteric and renal artery blood flows and cardiac output. In addition, YM099 (1-10 micrograms/kg i.v.) increased large conductive coronary artery vessel diameter as well as coronary artery blood flow. In conscious dogs, YM099 (100 micrograms/kg i.v.) also increased the diameter of large conductive and small resistive coronary arteries. In conclusion, YM099 is a potent vasodilator agent, with particularly pronounced effects on the coronary artery. These effects of YM099 may be mediated by the opening of ATP-sensitive K+ channels.
Uchida
W
W
Cardiovascular and Atherosclerosis Research Laboratories, Yamanouchi Institute for Drug Discovery Research, Ibaraki, Japan.
Hirano
Y
Y
Taguchi
T
T
Masuda
N
N
Shirai
Y
Y
Satoh
N
N
Takenaka
T
T
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000008:administration & dosage / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D002339:Carotid Arteries / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D019806:Cromakalim; D003497:Cyclic N-Oxides / Q000008:administration & dosage / Q000494:pharmacology*; D004176:Dipyridamole / Q000008:administration & dosage / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005263:Femoral Artery / Q000187:drug effects; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology; D010069:Oxadiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology; D012077:Renal Artery / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D001578:Benzopyrans; D003497:Cyclic N-Oxides; D010069:Oxadiazoles; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; C091804:YM 099; D019806:Cromakalim; D004176:Dipyridamole; D000255:Adenosine Triphosphate; D005996:Nitroglycerin; D005905:Glyburide