Chronotropic and inotropic effects of a new angiotensin converting enzyme inhibitor, MC-838 (altiopril calcium), on the dog heart.
The effects of calcium (-)-N-[(S)-3(N-cyclohexylcarbonyl-D-alanyl)-thio]-2-methylpropion] -L- prolinate (MC-838, altiopril calcium), an inhibitor of angiotensin converting enzyme, were investigated in 9 isolated atrial preparations and 7 intact anesthetized donor dogs. In 7 intact dogs, 1-10 mg/Kg of MC-838 caused a decrease in systemic blood pressure, but no significant influence on heart rate was observed. At the same time, in isolated atria perfused with donor's blood, significant increases in developed tension and slight increases in sinus rate were observed with 3 and 10 mg/Kg of MC-838. Intraarterial MC-838 at 10-300 micrograms did not induce significant cardiac effects and MC-838 at 1-3 mg caused an increase in developed tension and a slight increase in sinus rate. The positive inotropic and chronotropic effects were not blocked by adequate doses of propranolol, which significantly blocked norepinephrine-induced positive chronotropic and inotropic effects. It is concluded that a large amount of MC-838 has slight cardiotonic properties which are not mediated via a beta-adrenergic mechanism.
Chiba
S
S
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Furukawa
Y
Y
Saegusa
K
K
Ohba
Y
Y
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011392:Proline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D013268:Stimulation, Chemical
D000806:Angiotensin-Converting Enzyme Inhibitors; C048961:MC 838; D011392:Proline