NSU-MD Faculty Articles

Title

Myocardial adenosine, flow, and metabolism during adenosine antagonism and adrenergic stimulation.

ISBN or ISSN

0002-9513

Publication Title

The American journal of physiology

Volume

264

Issue

1 Pt 2

Publication Date / Copyright Date

1-1-1993

First Page

H61

Last Page

H70

Publisher

American Physiological Society

DOI Number

10.1152/ajpheart.1993.264.1.H61

Abstract

Relationships between interstitial transudate adenosine and coronary flow and between global adenosine formation and cytosolic metabolism were examined in constant-pressure perfused guinea pig hearts during norepinephrine (NE) stimulation and adenosine antagonism with 10 microM 8-phenyltheophylline. Basal coronary flow was 5.7 ml.min-1 x g-1, and transudate and venous adenosine levels were approximately 0.26 and 0.06 microM, respectively. During 10 min of NE stimulation (15 nM), coronary flow and adenosine levels increased, the phosphocreatine-to-inorganic phosphate ratio ([PCr]/[Pi]) declined, and ATP and pH remained stable. Despite phasic release of adenosine, coronary flow correlated dose dependently with transudate adenosine, and adenosine release was inversely related to [PCr]/[Pi] under all conditions. 8-Phenyltheophylline infusion attenuated functional hyperemia by approximately 40%, enhanced the fall in [PCr]/[Pi], and potentiated elevations in transudate and venous adenosine. Similar results and correlations were obtained in hearts perfused at a constant-flow of 5.7 ml.min-1 x g-1, although stimulated adenosine levels and metabolic changes were greater and contractile responses smaller. These data indicate that: 1) endogenous adenosine plays a primary role in functional hyperemia in perfused guinea pig heart; 2) global adenosine formation appears related to phosphorylation status; and 3) adenosine receptor antagonism enhances metabolic disturbances during adrenergic stimulation and markedly potentiates adenosine release, indicating that the functional effects of antagonists may significantly underestimate the dilatory role of endogenous adenosine.

Disciplines

Medicine and Health Sciences

Keywords

Adenosine, Animals, Coronary Circulation, Extracellular Space, Exudates and Transudates, Guinea Pigs, Hemodynamics, In Vitro Techniques, Male, Myocardium, Norepinephrine, Perfusion, Phosphorylation, Sympathomimetics, Theophylline

Peer Reviewed

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