Document Detail

Changes in extracellular pH and myocardial ischaemia alter the cardiac effects of diadenosine tetraphosphate and pentaphosphate.
MedLine Citation:
PMID:  11588119     Owner:  NLM     Status:  MEDLINE    
1. The structural conformation of diadenosine tetraphosphate (Ap(4)A) and pentaphosphate (Ap(5)A) has been reported to alter as pH is reduced. As such, it is possible that the cardiac effects of Ap(4)A and Ap(5)A vary during acidosis and myocardial ischaemia due to changes in ligand structure, receptor proteins or intracellular signalling. 2. We investigated whether the cardiac electrophysiological and coronary vasomotor effects of Ap(4)A and Ap(5)A are preserved under conditions of extracellular acidosis (pH 6.5) and alkalosis (pH 8.5) and whether Ap(4)A has any electrophysiological or antiarrhythmic effects during ischaemia. 3. Transmembrane right ventricular action potentials, refractory periods and coronary perfusion pressure were recorded from isolated, Langendorff-perfused guinea-pig hearts under constant flow conditions. The effects of 1 nM and 1 microM Ap(4)A and Ap(5)A were studied at pH 7.4, 6.5 and 8.5. The effects of 1 microM Ap(4)A were studied during global low-flow ischaemia and reperfusion. 4. At pH 7.4, Ap(4)A and Ap(5)A increased action potential duration (APD(95)) and refractory period (RP) and reduced coronary perfusion pressure. The electrophysiological effects were absent at pH 6.5 while the reductions in perfusion pressure were attenuated. At pH 8.5, Ap(4)A increased RP but the effects of Ap(4)A and Ap(5)A on perfusion pressure were attenuated. During ischaemia, Ap(4)A had no antiarrhythmic or electrophysiological effects. 5. These data demonstrate the importance of extracellular pH in influencing the effects of Ap(4)A and Ap(5)A on the heart and indicate that any potentially cardioprotective effects of these compounds during normal perfusion at physiological pH are absent during ischaemia.
B M Stavrou; C Beck; N A Flores
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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:  134     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2001 Oct 
Date Detail:
Created Date:  2001-10-05     Completed Date:  2001-12-05     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  639-47     Citation Subset:  IM    
Academic Cardiology Unit, National Heart and Lung Institute, Imperial College School of Medicine, London.
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MeSH Terms
Action Potentials / drug effects,  physiology
Dinucleoside Phosphates / pharmacology*,  therapeutic use
Extracellular Space / drug effects*,  physiology
Guinea Pigs
Hydrogen-Ion Concentration
Myocardial Ischemia / drug therapy,  metabolism*,  physiopathology
Myocardial Reperfusion / methods
Platelet Aggregation Inhibitors / pharmacology*,  therapeutic use
Vasoconstrictor Agents / pharmacology*,  therapeutic use
Reg. No./Substance:
0/Dinucleoside Phosphates; 0/Platelet Aggregation Inhibitors; 0/Vasoconstrictor Agents; 50304-44-4/P(1),P(5)-di(adenosine-5'-)pentaphosphate; 5542-28-9/diadenosine tetraphosphate

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