Arterial and venous vasodilator actions of RS-1893, a novel cardiotonic agent, in the hindlimb preparation of the dog.
RS-1893, an orally active cardiotonic agent, has been suggested to dilate venous blood vessels, because it markedly decreases central venous pressure in anesthetized dogs. In order to evaluate venous vasodilator action of the agent, we measured hindlimb volume (HLV) in anesthetized dogs using a plethysmographic technique. RS-1893 (1-10 micrograms/kg, i.v.) produced dose-dependent increases in HLV, femoral blood flow, and left ventricular (LV)dP/dt, and a decrease in central venous pressure (CVP). In another series of experiments, we autoperfused the hindlimb with a constant flow and injected the drugs intraarterially (i.a.) to separately evaluate arterial and venous vasodilator actions. In this preparation, a decrease in perfusion pressure and an increase in HLV were considered to reflect arterial vasodilatation and venous vasodilatation, respectively. RS-1893 (0.3-3 micrograms i.a.) produced a dose-dependent increase in HLV and a decrease in perfusion pressure. Comparison of doses which increased HLV by 0.3 ml revealed that RS-1893 was about 20 times more potent than milrinone. The arterial vasodilator action of RS-1893 was about 15 times more potent than that of milrinone. We conclude that RS-1893 is a potent venous and arterial vasodilator with cardiotonic activity.
Miyake
S
S
Biological Research Laboratories, Sankyo Co. Ltd., Tokyo, Japan.
Shiga
H
H
Koike
H
H
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply*; D007262:Infusions, Intravenous; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D009025:Morpholines / Q000008:administration & dosage / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology; D011724:Pyridazines / Q000008:administration & dosage / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D014665:Vasodilator Agents
D002316:Cardiotonic Agents; D009025:Morpholines; D011724:Pyridazines; D014665:Vasodilator Agents; C058563:RS 1893; D005996:Nitroglycerin