Antecedent sympathetic stimulation alters time course of chronotropic response to vagal stimulation in dogs

T. Yang, J. B. Senturia and M. N. Levy Department of Investigative Medicine, Mt. Sinai Medical Center, Case Western Reserve University, Cleveland 44106. We determined the influence of antecedent sympathetic stimulation on the chronotropic responses of the heart to 10-s strains of vagal stimulation in anesthetized dogs. We used the reciprocal of the slope (m-1) of the initial portion of the vagal response as an index of the time required for the response to reach steady state. In one group of 11 animals, we found that the onset of the response to the vagal stimulation was progressively blunted as we increased the frequency and duration of the antecedent sympathetic stimulation; that is, m-1 increased from 0 to 8.13 +/- 2.75 (SE) and from 0 to 8.22 +/- 2.26, respectively. In three other animals, an antecedent infusion of norepinephrine had a blunting effect that resembled that of antecedent sympathetic stimulation. In 11 other animals, m-1 significantly decreased as we prolonged the elapsed time from the end of sympathetic stimulation to the beginning of vagal stimulation. In six other animals, m-1 was not affected by antecedent atrial pacing at frequencies that were equivalent to those elicited by antecedent sympathetic stimulations. The blunting effect of antecedent sympathetic stimulation was abolished by propranolol administration (1 mg/kg), but it was not affected appreciably by phentolamine administration (2 mg/kg). We conclude that the major blunting effect of antecedent sympathetic stimulation is mediated postjunctionally (i.e., at the level of the automatic cells in the heart.