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.