Antagonistic influences of dibutyryl cyclic AMP and dibutyryl cyclic GMP on the beating rate of cultured mouse myocardial cells.

Cultured myocardial cells obtained from neonatal mouse ventricles beat spontaneously and rhythmically. Norepinephrine and dibutyryl cyclic AMP accelerated the rate of spontaneous beating. Dibutyryl cyclic GMP slightly decreased the rate of spontaneous beating. The acceleration of the beating rate of cultured myocardial cells by norepinephrine or dibutyryl cyclic AMP was counteracted by dibutyryl cyclic GMP. Preincubation of cultured myocardial cells with dibutyryl cyclic GMP prevented the positive chronotropic effect of dibutyryl cyclic AMP.     

Effects of dibutyryl cyclic AMP on ventricular vulnerability during atrioventricular block in dog.

The effects of dibutyryl cyclic AMP (DBcAMP) on ventricular vulnerability during complete atrioventricular block (CAVB) were studied one week after transarterial electrical ablation of the AV junction in 18 closed-chest dogs. All dogs exhibited CAVB and a stable ventricular escape rhythm with a mean cycle length of 1812 +/- 638 ms. After the administration of DBcAMP at a rate of 0.1 mg/kg/min for 30 min, the ventricular cycle length was significantly shortened, and the QTc interval was slightly prolonged, although the QT interval did not change. The ventricular fibrillation threshold after the administration of DBcAMP was significantly increased (from 12.2 +/- 3 84 to 18.4 +/- 5.08 mA, p less than 0.01). Thus, it was demonstrated that DBcAMP exhibited suppressive effects on the ventricular vulnerability in the experimentally induced CAVB.     

Effects of a new 1,3-thiazole Derivative ZSY-39 on force of contraction and cyclic AMP content in canine ventricular muscle

Summary A newly synthesized 1,3-thiazole derivative ZSY-39 increased the force of contraction in a concentrationdependent manner in association with elevation of tissue cyclic AMP levels in the isolated canine ventricular trabeculae electrically driven at 0.5 Hz at 37°C. ZSY-39 shortened the duration of isometric contractions mainly by abbreviation of the relaxation time. The maximal response to and EC₅₀ of ZSY-39 were 0.7 (isoproterenol=1.0) and 4.6×10^–5 M. Bupranolol (3×10^–7 M) did not affect the positive inotropic effect of ZSY-39. The time course of increases in the force of contraction induced by ZSY-39 (10^–4 M) coincided with that of cyclic AMP accumulation. The concentration-response curve for the increase in the force of contraction produced by ZSY-39 was superimposable on that of the elevation of cyclic AMP levels. Carbachol (3×10^–6 M) shifted the concentration-response curve for the increase in force by ZSY-39 to the right and downward, and decreased the accumulation of cyclic AMP induced by ZSY-39 (10^–4 M). ZSY-39 (10^–5 M) enhanced significantly the positive inotropic effect of isoproterenol. The relationship between the force of contraction and cyclic AMP levels after the administration of ZSY-39 was not modified by the addition of carbachol or isoproterenol. These findings indicate that cyclic AMP plays an important role in the positive inotropic effect of ZSY-39 on canine ventricular muscle.