. High plasma norepinephrine attenuates the dynamic heart rate response to vagal stimulation. Am J Physiol Heart Circ Physiol 284: H2412-H2418, 2003. First published February 21, 2003 10.1152/ajpheart.00660.2002To better understand the pathophysiological significance of high plasma norepinephrine (NE) concentration in regulating heart rate (HR), we examined the interactions between high plasma NE and dynamic vagal control of HR. In anesthetized rabbits with sinoaortic denervation and vagotomy, using a binary white noise sequence (0-10 Hz) for 10 min, we stimulated the right vagus and estimated the transfer function from vagal stimulation to HR response. The transfer function approximated a first-order low-pass filter with pure delay. Infusion of NE (100 g ⅐ kg Ϫ1 ⅐ h Ϫ1 iv) attenuated the dynamic gain from 6.2 Ϯ 0.8 to 3.9 Ϯ 1.2 beats ⅐ min Ϫ1 ⅐ Hz Ϫ1 (n ϭ 7, P Ͻ 0.05) without affecting the corner frequency or pure delay. Simultaneous intravenous administration of phentolamine (1 mg ⅐ kg Ϫ1 ⅐ h Ϫ1 ) and NE (100 g ⅐ kg Ϫ1 ⅐ h Ϫ1 ) abolished the inhibitory effect of NE on the dynamic gain (6.3 Ϯ 0.8 vs. 6.4 Ϯ 1.3 beats ⅐ min Ϫ1 ⅐ Hz Ϫ1 , not significant, n ϭ 7). The inhibitory effect of NE at infusion rates of 10, 50, and 100 g ⅐ kg Ϫ1 ⅐ h
Ϫ1on dynamic vagal control of HR was dose-dependent (n ϭ 5).In conclusion, high plasma NE attenuated the dynamic HR response to vagal stimulation, probably via activation of ␣-adrenergic receptors on the preganglionic and/or postganglionic cardiac vagal nerve terminals. systems analysis; transfer function; ␣-adrenergic receptors; heart rate variability; rabbit HEART RATE (HR) is mainly regulated by the sympathetic and parasympathetic nervous systems. Sympathetic activation and/or vagal withdrawal increases HR, whereas sympathetic withdrawal and/or vagal activation decreases HR. Accordingly, information on the mean level of HR alone does not allow a separate estimate of efferent activities of the two divisions of the autonomic nervous system. In contrast, information on the dynamic HR response has been considered useful in assessing vagal efferent nerve activity separately from sympathetic efferent nerve activity, because dynamic HR regulation is much faster via the vagal system than via the sympathetic system (3, 12). Accordingly, the high-frequency (HF) component (Ͼ0.15 Hz in humans) of HR variability (HRV) might reflect the cardiac vagal efferent nerve activity (2, 23). However, this notion is simplistic, in that it disregards interactions between the sympathetic and vagal systems.Complex sympathovagal interactions are known to occur in regulation of HR. An increase in the background sympathetic tone augmented the HR response to vagal nerve activity (16,17). Levy (17) termed this phenomenon an accentuated antagonism of the vagal control of HR. Accumulation of cAMP in the sinus nodal cells via activation of the postjunctional -adrenergic receptors contributed to the accentuated antagonism (20). On the other hand, activation of the prejunctional ␣-adrenergic receptors influenc...