Inotropic and Metabolic Effects of Dibutyryl Cyclic Adenosine 3‘, 5’‐Monophosphate in the Perfused Rat Heart

The isolated, working rat heart preparation was used to study whether dibutyryl cyclic adenosine 3′,5′‐monophosphate could reproduce the inotropic and nietabolic effects of catecholamines in the heart. The effects of dibutyryl cyclic AMP and adrenaline were studied in absence and presence of aβ‐receptor blocking agent (propranolol). Heart rate, cardiac output, peak systolic pressure, glycogen content, lactate production and concentrations of ATP and creatine‐phosphate were measured. Dibutyryl cyclic AMP (5×10‐3M and higher concentrations) evoked a positive inotropic effect as measured by an increase in peak systolic pressure, when the heart rate was kept constant by electrical stimulation. The nucleotide also produced a marked and concentration dependent (10‐5to10‐3) glycogenolytic effect. Propranolol (10‐5M) blocked the inotropic and glycogenolytic effects of adrenaline, but did not reduce the effects of dibutyryl cyclic AMP. The effects of adrenaline were seen already 1 min after its addition to the perfusion medium, while the effects of dibutyryl cyclic AMP were not seen until 3–5 min after addition of the nucleotide. In time course studies, no dissociation was observed between mechanical and metabolic effects of the nucleotide.