Document Detail

Coronary effects of diadenosine tetraphosphate resemble those of adenosine in anesthetized pigs: involvement of ATP-sensitive potassium channels.
MedLine Citation:
PMID:  8797146     Owner:  NLM     Status:  MEDLINE    
Diadenosine tetraphosphate (Ap4A) is an adenine nucleotide with vasodilatory properties. We examined the effects of Ap4A on coronary circulation in comparison with those of adenosine, its metabolite, in anesthetized pigs. Left atrial (LA) infusion of Ap4A at increasing doses of 100, 200, and 300 micrograms/kg/min increased coronary blood flow (CBF) and decreased systemic blood pressure (BP) and coronary vascular resistance (CVR). Ap4A had no effect on large epicardial coronary artery diameter (CoD). Likewise, LA infusion of adenosine at doses of 150 and 300 micrograms/kg/min increased CBF and decreased BP and coronary vascular resistance (CVR) but did not affect CoD. Therefore, the vasodilatory effects of Ap4A and adenosine were predominant in small coronary resistance vessels and negligible in large coronary arteries. Pretreatment with glibenclamide (2 mg/kg, intravenously, i.v.), a specific blocker of ATP-sensitive potassium channels (KATP), attenuated alterations of CBF, BP, and CVR induced by Ap4A and by adenosine. In contrast, treatment with cromakalim (0.5 microgram/kg/min i.v.), an activator of KATP, enhanced the coronary effects of Ap4A and adenosine. Therefore, the opening of KATP in the pig coronary circulation is involved in the in vivo vasodilatory effects of Ap4A and adenosine. Treatment with 8-phenyltheophylline (8-PT, 4 mg/kg i.v.), an adenosine receptor antagonist, suppressed CBF increases induced by Ap4A (20 micrograms/kg/min, intracoronarily, i.c.) and adenosine (5 micrograms/kg/min i.c.) by 68 and 90%, respectively. These findings suggest that the in vivo coronary effects of Ap4A are largely caused by the opening of KATP through rapid degradation to adenosine to activate adenosine receptors.
I Nakae; M Takahashi; A Takaoka; Q Liu; T Matsumoto; M Amano; A Sekine; H Nakajima; M Kinoshita
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  28     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1996 Jul 
Date Detail:
Created Date:  1997-01-06     Completed Date:  1997-01-06     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  124-33     Citation Subset:  IM    
First Department of Internal Medicine, Shiga University of Medical Science, Seta, Japan.
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MeSH Terms
Adenosine / pharmacology*
Coronary Vessels / drug effects*,  physiology
Dinucleoside Phosphates / blood,  pharmacology*
Dose-Response Relationship, Drug
Glyburide / pharmacology
Hemodynamics / drug effects*
Potassium Channels / drug effects*
Reg. No./Substance:
0/Dinucleoside Phosphates; 0/Potassium Channels; 10238-21-8/Glyburide; 5542-28-9/diadenosine tetraphosphate; 58-61-7/Adenosine

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