Time-course and frequency dependence of sympathetic stimulation-evoked inhibition of vagal effects at the sinus node

Abstract

Vagally-induced chronotropic responses have been shown to be inhibited after the termination of sympathetic stimulation. We sought to characterize the onset and time-course of the sympathetically evoked inhibition of vagal effects by measuring vagally induced chronotropic responses during concomitant sympathetic stimulation. In anesthetized dogs we recorded lead II of the electrocardiogram, arterial pressure and cardiac cycle length. In 7 dogs, the vagi were stimulated for 15 s every minute before, during and after 10-min trains of sympathetic stimulation. The sympathetic stimulation was applied at frequencies of 0.5, 1, 2, 5 and 10 Hz. During the 1, 2 and 5-Hz trains of sympathetic stimulation, the vagally induced changes in cycle length diminished progressively and thus, were less ( P < 0.001) at 3, 5 and 10 min compared with 1 min into the sympathetic stimulation. The magnitude of the attenuation of vagal effects on cycle length depended ( P < 0.001) on the frequency of sympathetic stimulation. To determine the role of alpha- and beta-adrenergic receptors, we measured vagally-induced changes in cycle length during 5-min trains of sympathetic stimulation (1, 2, 5, 10 Hz) in the presence and absence of phentolamine and propanolol ( n = 6). Both before and after combined alpha- and beta-adrenergic receptor blockade, the vagally-induced changes in cycle length decreased ( P < 0.03) progressively during the 1, 2, 5 and 10-Hz trains of sympathetic stimulation and the magnitude of the inhibition depended ( P < 0.002) on the frequency of sympathetic stimulation. These data show that the effects of short trains of vagal stimulation on cardiac cycle length are inhibited progressively during continuous trains of sympathetic stimulation before and after combined alpha- and beta-adrenergic receptor blockade. Thus, substances other than norepinephrine may contribute to the inhibition of cardiac vagal effects that occurs during a continuous train of sympathetic stimulation.