Document Detail

Influence of beta-adrenoceptor tone on the cardioprotective efficacy of adenosine A(1) receptor activation in isolated working rat hearts.
MedLine Citation:
PMID:  11015305     Owner:  NLM     Status:  MEDLINE    
This study investigated the role of beta-adrenoceptors in the cardioprotective and metabolic actions of adenosine A(1) receptor stimulation. Isolated paced (300 beats min(-1)) working rat hearts were perfused with Krebs-Henseleit solution containing 1.2 mM palmitate. Left ventricular minute work (LV work), O(2) consumption and rates of glycolysis and glucose oxidation were measured during reperfusion (30 min) following global ischaemia (30 min) as well as during aerobic conditions. Relative to untreated hearts, N(6)-cyclohexyladenosine (CHA, 0.5 microM) improved post-ischaemic LV work (158%) and reduced glycolysis and proton production (53 and 42%, respectively). CHA+propranolol (1 microM) had similar beneficial effects, while propranolol alone did not affect post-ischaemic LV work or glucose metabolism. Isoprenaline (10 nM) impaired post-ischaemic function and after 25 min ischaemia recovery was comparable with 30 min ischaemia in untreated hearts (41 and 53%, respectively). Relative to isoprenaline alone, CHA+isoprenaline improved recovery of LV work (181%) and reduced glycolysis and proton production (64 and 60%, respectively). In aerobic hearts, CHA, propranolol or CHA+propranolol had no effect on LV work or glucose oxidation. Glycolysis was inhibited by CHA, propranolol and CHA+propranolol (50, 53 and 52%, respectively). Isoprenaline-induced increases in heart rate, glycolysis and proton production were attenuated by CHA (85, 57 and 53%, respectively). The cardioprotective efficacy of CHA was unaffected by antagonism or activation of beta-adrenoceptors. Thus, the mechanism of protection by adenosine A(1) receptor activation does not involve functional antagonism of beta-adrenoceptors.
W R Ford; B I Jugdutt; G D Lopaschuk; R Schulz; A S Clanachan
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  131     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2000 Oct 
Date Detail:
Created Date:  2000-11-06     Completed Date:  2001-02-15     Revised Date:  2013-06-11    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  537-45     Citation Subset:  IM    
Cardiovascular Research Group, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada, T6G 2H7.
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MeSH Terms
Adrenergic beta-Agonists / pharmacology
Heart / drug effects*,  physiology
Isoproterenol / pharmacology
Myocardial Ischemia / metabolism*
Myocardial Reperfusion
Rats, Sprague-Dawley
Receptors, Adrenergic, beta / metabolism,  physiology*
Receptors, Purinergic P1 / metabolism*
Reg. No./Substance:
0/Adrenergic beta-Agonists; 0/Receptors, Adrenergic, beta; 0/Receptors, Purinergic P1; 7683-59-2/Isoproterenol

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