Involvement of alpha- and beta-adrenoceptors in the automaticity of the isolated guinea pig pulmonary vein myocardium

We examined the involvement of adrenoceptors in the automaticity of the pulmonary vein myocardium, which probably plays a crucial role in the generation of atrial fibrillation. The automatic activity of the myocardium in guinea pig pulmonary vein tissue preparations were monitored by contractile for...

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Published in:	Journal of pharmacological sciences Vol. 133; no. 4; pp. 247 - 253
Main Authors:	Irie, Masahiko, Tsuneoka, Yayoi, Shimobayashi, Mariko, Hasegawa, Nao, Tanaka, Yusuke, Mochizuki, Soh, Ichige, Sho, Hamaguchi, Shogo, Namekata, Iyuki, Tanaka, Hikaru
Format:	Journal Article
Language:	English
Published:	Japan Elsevier B.V 01-04-2017 Elsevier
Subjects:	Adrenoceptor Animals Atenolol - pharmacology Atrial Fibrillation - etiology Automaticity Carbazoles - pharmacology Carvedilol Guinea Pigs In Vitro Techniques Male Membrane Potentials - drug effects Membrane Potentials - physiology Myocardium Norepinephrine - antagonists & inhibitors Norepinephrine - pharmacology Prazosin - pharmacology Propanolamines - pharmacology Pulmonary vein Pulmonary Veins - physiology Receptors, Adrenergic, alpha - physiology Receptors, Adrenergic, beta - physiology Vasoconstriction - drug effects Vasoconstriction - physiology Automaticity Adrenoceptor Carvedilol Pulmonary vein
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Abstract	We examined the involvement of adrenoceptors in the automaticity of the pulmonary vein myocardium, which probably plays a crucial role in the generation of atrial fibrillation. The automatic activity of the myocardium in guinea pig pulmonary vein tissue preparations were monitored by contractile force or membrane potential measurement. In quiescent preparations, application of noradrenaline induced an automatic activity. The firing frequency was reduced by prazosin or atenolol. Methoxamine induced an automatic activity of low frequency, which was accelerated by further application of isoproterenol. In preparations driven at a constant frequency, noradrenaline, in the presence of atenolol, caused a depolarizing shift of the resting membrane potential and an increase in the slope of the diastolic depolarization. In contrast, in the presence of prazosin, noradrenaline had no effect on the slope, but caused acceleration of the late repolarization and a hyperpolarizing shift of the maximum diastolic potential. At clinically relevant concentrations, carvedilol significantly inhibited the noradrenaline-induced activity but bisoprolol did not. It was concluded that α1- and β1-adrenoceptor stimulation enhance automaticity through different mechanisms in the guinea pig pulmonary vein myocardium. Dual blockade of these adrenoceptors appears to be effective for suppressing noradrenaline-induced pulmonary vein automaticity and probably atrial fibrillation.
AbstractList	We examined the involvement of adrenoceptors in the automaticity of the pulmonary vein myocardium, which probably plays a crucial role in the generation of atrial fibrillation. The automatic activity of the myocardium in guinea pig pulmonary vein tissue preparations were monitored by contractile force or membrane potential measurement. In quiescent preparations, application of noradrenaline induced an automatic activity. The firing frequency was reduced by prazosin or atenolol. Methoxamine induced an automatic activity of low frequency, which was accelerated by further application of isoproterenol. In preparations driven at a constant frequency, noradrenaline, in the presence of atenolol, caused a depolarizing shift of the resting membrane potential and an increase in the slope of the diastolic depolarization. In contrast, in the presence of prazosin, noradrenaline had no effect on the slope, but caused acceleration of the late repolarization and a hyperpolarizing shift of the maximum diastolic potential. At clinically relevant concentrations, carvedilol significantly inhibited the noradrenaline-induced activity but bisoprolol did not. It was concluded that α1- and β1-adrenoceptor stimulation enhance automaticity through different mechanisms in the guinea pig pulmonary vein myocardium. Dual blockade of these adrenoceptors appears to be effective for suppressing noradrenaline-induced pulmonary vein automaticity and probably atrial fibrillation. We examined the involvement of adrenoceptors in the automaticity of the pulmonary vein myocardium, which probably plays a crucial role in the generation of atrial fibrillation. The automatic activity of the myocardium in guinea pig pulmonary vein tissue preparations were monitored by contractile force or membrane potential measurement. In quiescent preparations, application of noradrenaline induced an automatic activity. The firing frequency was reduced by prazosin or atenolol. Methoxamine induced an automatic activity of low frequency, which was accelerated by further application of isoproterenol. In preparations driven at a constant frequency, noradrenaline, in the presence of atenolol, caused a depolarizing shift of the resting membrane potential and an increase in the slope of the diastolic depolarization. In contrast, in the presence of prazosin, noradrenaline had no effect on the slope, but caused acceleration of the late repolarization and a hyperpolarizing shift of the maximum diastolic potential. At clinically relevant concentrations, carvedilol significantly inhibited the noradrenaline-induced activity but bisoprolol did not. It was concluded that α - and β -adrenoceptor stimulation enhance automaticity through different mechanisms in the guinea pig pulmonary vein myocardium. Dual blockade of these adrenoceptors appears to be effective for suppressing noradrenaline-induced pulmonary vein automaticity and probably atrial fibrillation.
Author	Ichige, Sho Shimobayashi, Mariko Mochizuki, Soh Irie, Masahiko Tsuneoka, Yayoi Hasegawa, Nao Hamaguchi, Shogo Tanaka, Yusuke Namekata, Iyuki Tanaka, Hikaru
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Keywords	Automaticity Adrenoceptor Carvedilol Pulmonary vein
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Snippet	We examined the involvement of adrenoceptors in the automaticity of the pulmonary vein myocardium, which probably plays a crucial role in the generation of...
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SubjectTerms	Adrenoceptor Animals Atenolol - pharmacology Atrial Fibrillation - etiology Automaticity Carbazoles - pharmacology Carvedilol Guinea Pigs In Vitro Techniques Male Membrane Potentials - drug effects Membrane Potentials - physiology Myocardium Norepinephrine - antagonists & inhibitors Norepinephrine - pharmacology Prazosin - pharmacology Propanolamines - pharmacology Pulmonary vein Pulmonary Veins - physiology Receptors, Adrenergic, alpha - physiology Receptors, Adrenergic, beta - physiology Vasoconstriction - drug effects Vasoconstriction - physiology
Title	Involvement of alpha- and beta-adrenoceptors in the automaticity of the isolated guinea pig pulmonary vein myocardium
URI	https://dx.doi.org/10.1016/j.jphs.2017.03.003 https://www.ncbi.nlm.nih.gov/pubmed/28410967 https://search.proquest.com/docview/1888683891 https://doaj.org/article/7886e1ef4bd74834b5f378fa4060ac3b
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