Mechanism of Sympathomimetic Responses of Isolated Guinea‐pig Atria to Nicotine and Dimethylphenylpiperazinium Iodide

Bhagat, B.; Robinson, Ina M.; West, William L.

doi:10.1111/j.1476-5381.1967.tb02153.x

Cited by 12 publications

(7 citation statements)

References 14 publications

(13 reference statements)

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“…Further more, 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>…”

mentioning

confidence: 99%

Pharmacologic Analysis of Nicotine and Dimethylphenylpiperazinium on Pacemaker Activity of the Sa Node in the Dog

et al. 1972

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mentioning

confidence: 99%

Pharmacologic Analysis of Nicotine and Dimethylphenylpiperazinium on Pacemaker Activity of the Sa Node in the Dog

et al. 1972

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“…As shown by other workers (Chiang and Leaders, 1965;Bhagat, 1966;Bhagat et al, 1967;Misu and Kirpekar, 1968), nicotine also produced a biphasic effect on the heart rate, that is an initial negative chronotropic phase followed by a positive one. Our results suggest that nicotine also releases both acetylcholine and norepinephrine, which increase the levels of cyclic GMP and cyclic AMP, respectively.…”

Section: Discussionmentioning

confidence: 70%

Effect of acetylcholine on the norepinephrine-induced positive chronotropy and increase in cyclic nucleotides of isolated rabbit sinoatrial node.

Taniguchi¹,

Fujiwara²,

Lee³

et al. 1979

Circulation Research

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SUMMARY Transmural stimulation of, or application of nicotine to, the isolated rabbit sinoatrial (SA) node resulted in initial negative and late positive chronotropy. Simultaneous application of acetylcholine and norepinephrine produced a similar biphasic chronotropic effect. These procedures produced an initial increase in cyclic guanosine 3':5'-monophosphate (cyclic GMP) and a delayed elevation in cyclic adenosine 3':5'-monophosphate (cyclic AMP). The initial and late effects on rate and nucleotide levels were inhibited by pretreatment with atropine and propranolol, respectively. Pretreatment with atropine shortened the time of maximum increase in cyclic AMP level and heart rate from 3 to 1 minute after the simultaneous application of acetylcholine and norepinephrine and enhanced the positive chronotropic effect. Physostigmine prolonged the duration of the increase in cyclic GMP and negative chronotropic effect after the simultaneous application. These results suggest that when acetylcholine and norepinephrine are present simultaneously in the SA node region, the former interacts predominantly with muscarinic receptors and stimulates the cyclic GMP system, which in effect delays the cyclic AMP elevation and reduces the positive chronotropic effect of norepinephrine. However, these effects of acetylcholine cannot be explained solely on the basis of changes in the cyclic GMP level, because sodium nitroprusside produced a marked elevation of the cyclic GMP levels without decreasing the heart rate and did not affect the norepinephrine-induced increase in pacemaker rate and cyclic AMP. Sodium nitroprusside may affect cyclic GMP pools other than those susceptible to acetylcholine. These cyclic GMP pools may not exert chronotropic effects. Ore Res 45: 493-504, 1979 THE sinoatrial (SA) node of the mammalian heart receives its nerve supply from both the parasympathetic (James and Spence, 1966) and sympathetic (Shindler et al., 1968;Taniguchi et al., 1977) divisions of the autonomic nervous system and, although these two nerves reciprocally regulate the heart rate, the parasympathetic nerve predominates (Voile and Koelle, 1975). Carrier and Bishop (1972) found that when both acetylcholine and norepinephrine were present, the former had a greater effect on heart rate.Previously Taniguchi et al., 1977) that cyclic adenosine 3':5'-monophosphate (cyclic AMP) in the SA node was involved in the positive chronotropic effect of norepinephrine. However, George and associates (1970) snowed that perfusion of the rat heart with acetylcholine resulted in an elevation of cyclic guanosine 3':5'-monophosphate (cyclic GMP) level which paralleled the negative inotropic and chronotropic effects. Watanabe and Besch (1975) suggested that, in the isolated guinea pig ventricle, cyclic GMP mediates the antiadrenergic effects of acetylcholine by specifically antagonizing the inotropic actions of cyclic AMP.Recently, Diamond et al. (1977) showed that sodium nitroprusside markedly increased cat atrial cyclic GMP levels but did not decrease ...

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“…The positive cardiac effects of nicotine are caused by a release of NE, which is attributed to stimulation of nicotinic recep tors at sympathetic nerve terminals (4,16,17). In the present experiments, the positive chro notropic and inotropic responses to stimula tion of intracardiac sympathetic nerves or NE injection were not inhibited by eperisone.…”

Section: Discussionmentioning

confidence: 99%

Anti-Nicotinic and Anti-Muscarinic Actions of Eperisone in the Isolated Canine Atrium.

et al. 1991

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ABSTRACT-The effects of eperisone, an antispastic agent, on the chronotropic and inotropic responses to acetylcholine, nicotine or stimulation of intracardiac autonomic nerves were evaluated in isolated, blood-perfused canine atrium. Eperisone (10-300,ug) injected into the sinus node artery of the isolated atrium produced dose-related nega tive chronotropic and inotropic effects, which were not affected by atropine. In the same doses, eperisone inhibited the negative chronotropic and inotropic responses to an injection of acetylcholine and intracardiac parasympathetic stimulation. Eperisone also suppressed the negative followed by positive cardiac responses to nicotine, but did not modify the positive responses to intracardiac sympathetic stimulation or nor epinephrine. The inhibitory effect persisted much longer for the responses to nicotine or parasympathetic stimulation than for those to acetylcholine. These results suggest that eperisone at doses that induce direct cardiac depressant effects exerts its blocking action on nicotinic receptors at parasympathetic ganglia and sympathetic nerve termi nals and on muscarinic receptors at the effector cells in the dog heart.

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Mechanism of Sympathomimetic Responses of Isolated Guinea‐pig Atria to Nicotine and Dimethylphenylpiperazinium Iodide

Cited by 12 publications

References 14 publications

Pharmacologic Analysis of Nicotine and Dimethylphenylpiperazinium on Pacemaker Activity of the Sa Node in the Dog

Pharmacologic Analysis of Nicotine and Dimethylphenylpiperazinium on Pacemaker Activity of the Sa Node in the Dog

Effect of acetylcholine on the norepinephrine-induced positive chronotropy and increase in cyclic nucleotides of isolated rabbit sinoatrial node.

Anti-Nicotinic and Anti-Muscarinic Actions of Eperisone in the Isolated Canine Atrium.

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