1. Cardiovascular effects of YM099, a novel K+ channel opener, in anesthetized and conscious dogs
- Author
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Wataru Uchida, Taku Taguchi, Noriyuki Masuda, Toichi Takenaka, Noboru Satoh, Yusuke Hirano, and Yasuko Shirai
- Subjects
Male ,Cromakalim ,medicine.medical_specialty ,Cardiac output ,Potassium Channels ,Vasodilator Agents ,Blood Pressure ,Vasodilation ,Cardiovascular System ,Cyclic N-Oxides ,Nitroglycerin ,Adenosine Triphosphate ,Dogs ,Renal Artery ,Heart Rate ,Coronary Circulation ,medicine.artery ,Internal medicine ,Glyburide ,Heart rate ,medicine ,Animals ,Benzopyrans ,Pyrroles ,Cardiac Output ,Renal artery ,Pharmacology ,Oxadiazoles ,Dose-Response Relationship, Drug ,business.industry ,Dipyridamole ,Blood flow ,Mesenteric Arteries ,Femoral Artery ,Coronary arteries ,Carotid Arteries ,medicine.anatomical_structure ,Mean blood pressure ,Injections, Intravenous ,Cardiology ,Female ,Vascular Resistance ,business ,Blood Flow Velocity ,Artery - Abstract
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.
- Published
- 1994