Document Detail

Modulation of pacemaker activity in sheep cardiac Purkinje fibers by stimulation of beta-adrenoceptor subtypes.
MedLine Citation:
PMID:  9062649     Owner:  NLM     Status:  MEDLINE    
The electrophysiological effects mediated by beta 1- and beta 2-adrenoceptors in spontaneously active sheep cardiac Purkinje fibers were investigated using the non-selective agonist (-)-isoproterenol (IPN) and the selective agonists (-)-noradrenaline (beta 1) and procaterol (beta 2) in the absence and presence of the selective antagonists bisoprolol (beta 1) and ICI 118,551 (beta 2). IPN (0.01 mumol/l) increased the spontaneous rate by 54% and the slope of diastolic depolarization by 68% of the respective control values. Further, IPN increased the action potential duration at -20 mV (APD -20 mV) from 96 to 154 ms, reduced the APD-70 mV by 17% and the duration of the diastole by 39% and slightly hyperpolarized the maximum diastolic potential. These effects were partially inhibited by ICI 118,551 (0.03 mumol/l), diminished by bisoprolol (0.1 mumol/l) and almost completely blocked by the combination of both antagonists. Concentration response curves of IPN were influenced by the selective antagonists as follows: ICI 118,551 (0.03 mumol/l) shifted the curves to the right by 0.2-0.4 log units and increased the slope factor. Bisoprolol (0.1 mumol/l) induced a greater shift to the right by 1.1-1.5 log units. Combination of bisoprolol with ICI 118,551 shifted the curves to the right by 1.5-1.7 log units. Noradrenaline (0.3 mumol/l) elicited similar actions as IPN. Bisoprolol (0.1 mumol/l) shifted the concentration response curves of noradrenaline to the right by 1.1-1.9 log units. Actions of procaterol (0.1 mumol/l) were weak, attained only 15-35% of the maximal effects of IPN and could be blocked by ICI 118,551 (0.03 mumol/l). These results show that the increase of pacemaker activity induced by catecholamines in sheep cardiac Purkinje fibers is predominantly mediated by stimulation of beta 1-receptors. However, contribution of beta 2-receptor mediated effects could be demonstrated.
U Thome; F Berger; U Borchard; D Hafner
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Basic research in cardiology     Volume:  92     ISSN:  0300-8428     ISO Abbreviation:  Basic Res. Cardiol.     Publication Date:  1997 Feb 
Date Detail:
Created Date:  1997-05-22     Completed Date:  1997-05-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0360342     Medline TA:  Basic Res Cardiol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  25-34     Citation Subset:  IM    
Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany.
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MeSH Terms
Adrenergic alpha-Agonists / pharmacology
Adrenergic beta-Agonists / pharmacology
Adrenergic beta-Antagonists / pharmacology
Bisoprolol / pharmacology
Dose-Response Relationship, Drug
Heart Conduction System / drug effects,  physiology*
Isoproterenol / pharmacology
Norepinephrine / pharmacology
Procaterol / pharmacology
Propanolamines / pharmacology
Purkinje Fibers / drug effects,  physiology*
Receptors, Adrenergic, beta-1 / metabolism*
Receptors, Adrenergic, beta-2 / metabolism*
Reg. No./Substance:
0/Adrenergic alpha-Agonists; 0/Adrenergic beta-Agonists; 0/Adrenergic beta-Antagonists; 0/Propanolamines; 0/Receptors, Adrenergic, beta-1; 0/Receptors, Adrenergic, beta-2; 51-41-2/Norepinephrine; 66722-44-9/Bisoprolol; 72332-33-3/Procaterol; 72795-19-8/ICI 118551; 7683-59-2/Isoproterenol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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