PHARMACOLOGIC ANALYSIS OF NICOTINE AND DIMETHYLPHENYLPIPERAZINIUM ON PACEMAKER ACTIVITY OF THE SA NODE IN THE DOG

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It is well known that nicotine and 1, 1-dimethyl-4-phenylpiperazinium (DMPP) have biphasic chronotropic responses both by stimulating the intracardiac parasympathetic ganglia and by liberating catecholamines locally (1-4). In 1967, Nadeau and James reported effects of nicotine on heart rate using a direct perfusion technique of the SA node in dogs (5). They showed that the negative chronotropic response to nicotine was abolished by treatment with atropine and that of the positive by either propranolol or hexamethonium. Furthermore, Bhagat et al. reported that nicotine-induced acceleration of sinus rate was inhibited by hexamethonium but the DMPP-induced one was not suppressed by hexamethonium in isolated guineapig atria (6).<BR> From the pharmacological point of view, it is of interest to investigate the chronotropic effects of nicotine and DMPP by utilization of blood-perfused SA node preparations of dogs. Previously Hashimoto and Chiba (7) demonstrated that tetrodotoxin was a selective blocking agent of nerve stimulation in the sinoatrial preparation and as such was a useful tool for excluding the effect of nerve excitation at peripheral organs. In this study, an attempt was made to analyse responses to nicotine and DMPP by use of tetrodotoxin in addition to autonomic drugs.<BR> Preliminary data from this study has previously been reported (8).
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