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1 Department of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, Suita, Osaka 565, Japan; and 2 Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37235
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 · min1 iv) increased the
dynamic gain of transfer function from 7.12 ± 0.67 to 12.4 ± 1.21 beats · min1 · Hz1
(P < 0.05) without
changing the corner frequency or the lag time. Similar augmentations
were observed when forskolin (5 µg · kg1 · min1
iv) or theophylline (20 mg/kg iv) was administered under conditions of
-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.
adenosine 3',5'-cyclic monophosphate; dynamic stimulation; Gaussian white noise; phosphodiesterase; systems analysis
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