NSU-MD Faculty Articles
Myocardial adenosine, flow, and metabolism during adenosine antagonism and adrenergic stimulation.
Publication Title
The American journal of physiology
Publisher
American Physiological Society
ISSN
0002-9513
Publication Date
1-1-1993
Keywords
Adenosine, Animals, Coronary Circulation, Extracellular Space, Exudates and Transudates, Guinea Pigs, Hemodynamics, In Vitro Techniques, Male, Myocardium, Norepinephrine, Perfusion, Phosphorylation, Sympathomimetics, Theophylline
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.
DOI
10.1152/ajpheart.1993.264.1.H61
Volume
264
Issue
1 Pt 2
First Page
H61
Last Page
H70
Disciplines
Medicine and Health Sciences
NSUWorks Citation
Headrick, J P; Ely, Stephen W.; Matherne, G P; and Berne, R M, "Myocardial adenosine, flow, and metabolism during adenosine antagonism and adrenergic stimulation." (1993). NSU-MD Faculty Articles. 73.
https://nsuworks.nova.edu/hpd_md_facarticles/73