Cholinergic-adrenergic antagonism in the induction of tachyarrhythmia by electrical stimulation in isolated rat atria.
Atrial tachyarrhythmias (AT) are the most common cardiac rhythm disturbance. In the present study, we analyzed the cholinergic-adrenergic interaction in the in vitro induction of cholinergic-dependent tachyarrhythmia by high-frequency electric stimulation. Tachyarrhythmia was evoked in isolated rat right atria by trains of electric stimuli. Atrial response was expressed as the tachyarrhythmia induction index (ATI, i.e. the fraction of applied trains that resulted in arrhythmia induction). ATI was reversibly increased by 0.6 microM carbachol (CCh), which also decreased atrial spontaneous rate (ASR). In contrast, 10 nM isoproterenol (ISO), 100 microM tyramine and the phosphodiesterase inhibitor isobutyl-methylxanthine (IBMX, 100 microM) increased ASR and decreased ATI. Amiodarone (AMI, 10 microM) reduced ATI in the presence and absence of CCh. Further CCh addition restored ATI in atria treated with either IBMX or AMI, but not when both compounds were present. Increase in ATI by CCh in atria pretreated with IBMX plus ISO was significantly attenuated by 3 mM NaF. The antagonism between cholinergic muscarinic and beta-adrenergic receptor stimulation (the former facilitating and the latter inhibiting tachyarrhythmia installation) possibly involves regulation of the phosphorylation status of adenosine cyclic 3'-5'-monophosphate (cAMP)-dependent protein kinase substrates. Additionally, cAMP-independent, AMI-sensitive mechanism stimulated by CCh (possibly muscarinic-dependent K(+) current activation) seems to contribute to AT facilitation.
Zafalon
Nivaldo
N
Departamento de Engenharia Biomédica, Faculdade de Engenharia Elétrica e de Computação and Centro de Engenharia Biomédica, Universidade Estadual de Campinas, Caixa Postal 6040, Campinas, SP 13084 971, Brazil.
Bassani
José W M
JW
Bassani
Rosana A
RA
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000638:Amiodarone / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004594:Electrophysiology; D006325:Heart Atria / Q000473:pathology*; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism; D012969:Sodium Fluoride / Q000494:pharmacology; D013610:Tachycardia / Q000378:metabolism*; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D018679:Cholinergic Agonists; D010726:Phosphodiesterase Inhibitors; D011941:Receptors, Adrenergic; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D002217:Carbachol; D012969:Sodium Fluoride; D000242:Cyclic AMP; D010744:Phosphoric Monoester Hydrolases; D000638:Amiodarone; D015056:1-Methyl-3-isobutylxanthine