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To elucidate the role of the autonomic nervous system in modulating the effect of verapamil on sinus node (SN) function, five volunteers were repeatedly studied both with and without prior autonomic blockade.Veraparnil alone (0.i mg/kg i.v.) caused a significant decrease in spontaneous cycle length (SCL) from 1104 _+ lll.6msec to 891_ 67msec (mean _ S.D., P < 0.01). After pretreatment with propranolol (0.I mg/kg i.v.) and atropine (0.02 mglkg i.v.), verapamil had an opposite effect on SCL with an increase from 686 + 66 msec (pre) to a plateau alternating between 690 msee and 712 msec (post) (P < 0.01). Pretreatment with propranolol alone did not prevent the decrease in SCL after injection of verapamil; SCL changed from 1295 +__ 85 msec to 1020 ___ 87 msec (P < 0.01). The extent of this decrease in SCL was similar to the effect of verapamil without any pretreatment. After atropine pretreatment, there was a small but insignificant decrease in SCL during the first five minutes; whereas later SCL increased.Verapamil led to a fall in blood pressure. After pretreatment with propranolol there was no significant change in blood pressure after injection of verapamil; whereas after pretreatment with either atropine alone or with propranolol and atropine there was a significant decrease in blood pressure.The results suggest that the autonomic nervous system plays an important part in modulating the effect of verapamil on SN function in man. The cardio-accelerating effect of verapamil is either provoked by a fall in blood pressure and a consecutive restraint of vagal innervation on the sinus node or a direct vagolytic action of the drug. An increase in sympathetic tone seems to be less important.In a recent study we were able to show that verapamil may have opposite effects on sinus node function depending on the integrity of the sinus node (1, 2). In patients with normal sinus node (SN) function it increased heart rate and had only slight effects on sinus node recovery time (SNRT). However, in those with presumably more advanced SN dysfunction, heart rate decreased and SNRT increased markedly. A similar opposite effect of verapamil on the sinus node was observed in two *) Supported in part by the Landesamt fiir Forschung, Nordrhein-Westfalen. 773

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