[Effects of fusaric acid and its derivative on the cardiovascular system].
The cardiovascular effects of fusaric acid, a dopamine-beta-hydroxylase (DBH) inhibitor and a hypotensive agent, and 5-(4'-chlorobutyl) picolinic acid, one of the most potent DBH inhibitors in fusaric acid derivatives, were investigated in anesthetized dogs. Fusaric acid (10-30 mg/kg) given intravenously caused immediately and dose-dependently a fall in blood pressure, an increase in heart rate, a stimulation of respiration, a marked increase in the rate of superior mesenteric arterial flow, and a decrease in the rate of femoral arterial flow. Fusaric acid (0.3-3 mg) given close-arterially caused a dose-dependent decrease in the sinus rate and in the developed tension in isolated blood-perfused sinoatrial node and papillary muscle preparations, respectively. For the superior mesenteric, renal, and femoral circulations which were perfused with blood, a close-arterial injection of fusaric acid (10-30 mg) increased in the rates of flow in a dose-dependent manner. 5-(4'-Chlorobutyl) picolinic acid showed similar responses as fusaric acid quantitatively or qualitatively. These results indicate that hypotension induced rapidly after intravenous administration of fusaric acid or 5-(4'-chlorobutyl) picolinic acid is not due to the enzyme inhibition, but rather to the direct depression of cardiac function and decrease in peripheral vascular resistance.
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D004285:Dogs; D005263:Femoral Artery / Q000187:drug effects; D005669:Fusaric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010848:Picolinic Acids / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D012077:Renal Artery / Q000187:drug effects; D012119:Respiration / Q000187:drug effects
D010848:Picolinic Acids; D005669:Fusaric Acid