Accumulation of cAMP augments dynamic vagal control of heart rate.

Recent investigations in our laboratory using a Gaussian white noise perturbation technique have shown that simultaneous sympathetic stimulation augmented the gain of the transfer function from vagal stimulation frequency to heart rate response. However, the mechanism of that augmentation remains to be elucidated. In this study, we examined in anesthetized rabbits how three pharmacological interventions known to cause intracellular accumulation of cAMP affected the transfer function. Isoproterenol (0.3 μg ⋅ kg-1 ⋅ min-1 iv) increased the dynamic gain of transfer function from 7.12 ± 0.67 to 12.4 ± 1.21 beats ⋅ min-1 ⋅ Hz-1( P < 0.05) without changing the corner frequency or the lag time. Similar augmentations were observed when forskolin (5 μg ⋅ kg-1 ⋅ min-1iv) or theophylline (20 mg/kg iv) was administered under conditions of β-adrenergic blockade. These results suggest that the accumulation of cAMP at postjunctional effector sites contributes, at least in part, to the sympathetic augmentation of the dynamic vagal control of heart rate.