Neuronal uptake affects dynamic characteristics of heart rate response to sympathetic stimulation

Recently, studies in our laboratory involving the use of a Gaussian white n oise technique demonstrated that the transfer function from sympathetic sti mulation frequency to heart rate (HR) response showed dynamic characteristi cs of a second-order low-pass filter. However, determinants for the charact eristics remain to be established. We examined the effect of an increase in mean sympathetic stimulation frequency and that of a blockade of the neuro nal uptake mechanism on the transfer function in anesthetized rabbits. We f ound that increasing mean sympathetic stimulation frequency from 1 to 4 Hz significantly (P < 0.01) decreased the dynamic gain of the transfer functio n without affecting other parameters, such as the natural frequency, lag ti me, or damping coefficient; In contrast, the administration of desipramine (0.3 mg/kg iv), a neuronal uptake blocking agent, significantly (P < 0.01) decreased both the dynamic gain and the natural frequency and prolonged the lag time. These results suggest that the removal rate of norepinephrine at the neuroeffector junction, rather than the amount of available norepineph rine, plays an important role in determining the low-pass filter characteri stics of the HR response to sympathetic stimulation.