Negative chronotropic effects of meglumine cyclic adenylate on heart

A new cyclic adenylate analog meglumine cyclic adenylate (MCA) 100 mg/kg iv markedly slowed the heart rates of anesthetized mice. rats. guinea pigs and ananesthetized rabbits and significantly prolonged the P-P intervals in the ECG. The negative chronotropic effects of MCA on the isolated right rabbit atria were dose dependent. The negative chronotropic effects of exogenous cAMP were consistent with that of MCA at the same concentration (2.21 mmol/L). An on-line microcomputer was used to analyze in real time the action potential parameters of the dominant pacemaker cells in the rabbit sinoatrial nodes. MCA or cAMP l.8 mmol/L significantly decreased the spontaneous firing frequencies, slowed the rate of diastolic depolarization and prolonged the action potential duration. MCA also antagonized the positive chronotropic action induced by isoprenallne 5 nmol/L in the sinoatrial nodes.