Functional and metabolic effects of bucladesine (dibutyryl cyclic AMP) in the working rat heart preparation: comparison with dopamine.
The effects of bucladesine (10(-4) and 3 x 10(-4) M) on cardiac function and energy metabolism were investigated in comparison with those of dopamine (3 x 10(-6) and 10(-5) M) in the working rat heart preparation. Bucladesine dose-dependently increased systolic pressure, cardiac work and coronary flow, but scarcely changed heart rate or cardiac output at 78 cm H2O perfusion pressure. Dopamine increased systolic pressure to a similar extent as bucladesine and also increased heart rate, cardiac work and coronary flow, but did not change cardiac output. Neither drug caused any changes in energy metabolites. At reduced perfusion pressure (15 cm H2O), bucladesine increased systolic pressure, coronary flow and cardiac output, but caused a decrease (at 10(-4) M) or a negligible change (at 3 x 10(-4) M) in heart rate. At 10(-4) M, there was only a slight change in energy metabolism, but at 3 x 10(-4) M, anaerobic metabolism was enhanced. Dopamine decreased systolic pressure and coronary flow and increased heart rate and cardiac work. Cardiac output increased transiently and, thereafter, decreased. Dopamine also enhanced anaerobic metabolism at both doses. The results suggest that both drugs exert similar effects at normal perfusion pressure, but after reduction of perfusion pressure, some differences occur between the two drugs, presumably due to acceleration of the heart rate and subsequent increase in cardiac work by dopamine.
Hashimoto
H
H
Research Institute, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Kunitada
S
S
Tamura
K
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006333:Heart Failure / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D010725:Phosphocreatine; D003994:Bucladesine; D000255:Adenosine Triphosphate; D004298:Dopamine