Effect of YM435, a novel dopamine DA1 receptor agonist, in a canine model of acute congestive heart failure.
1. The effects of YM435, a dopamine DA1 receptor agonist, were evaluated in a canine model of acute congestive heart failure. 2. The model was induced in open-chest anesthetized dogs by left anterior descending coronary artery ligation, volume loading, and intravenous infusion of angiotensin II. This resulted in a moderate and stable congestive heart failure characterized by reduction in cardiac output and increases in left ventricular end-diastolic pressure and total peripheral vascular resistance. 3. Intravenous infusion of YM435 (1 microgram/kg/min) significantly decreased left ventricular end-diastolic pressure, total peripheral vascular resistance and mean blood pressure and significantly increased cardiac output and renal blood flow in this model. 4. These results indicate that intravenous infusion of YM435 can improve hemodynamics and cardiac function in a canine model of acute congestive heart failure. YM435 may be a useful therapeutic agent for the treatment of congestive heart failure.
Yatsu
T
T
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd, Ibaraki, Japan. yatsu@yamanouchi.co.jp
Arai
Y
Y
Sudoh
K
K
Shibasaki
M
M
Uchida
W
W
Inagaki
O
O
Tanaka
A
A
Takenaka
T
T
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects*; D007546:Isoquinolines / Q000627:therapeutic use*; D008297:Male; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000378:metabolism; D044005:Tetrahydroisoquinolines; D014665:Vasodilator Agents / Q000627:therapeutic use*
D007546:Isoquinolines; D017447:Receptors, Dopamine D1; D044005:Tetrahydroisoquinolines; D014665:Vasodilator Agents; C098593:dopamine D1A receptor; C073504:zelandopam