Affiliation:
1. From the Institut für Physiologie, Medizinische Fakultät Carl Gustav Carus, TU Dresden (A.D., M.S.), and the Klinik für Kardiologie, Pneumologie, und Angiologie, Heinrich-Heine-Universität Düsseldorf (S.S., M.K.), Germany.
Abstract
Background
—Inhibitors of adenosine membrane transport cause vasodilation and enhance the plasma adenosine concentration. However, it is unclear why the plasma adenosine concentration rises rather than falls when membrane transport is inhibited. We tested the hypothesis that the cytosolic adenosine concentration exceeds the interstitial concentration under well-oxygenated conditions.
Methods and Results
—In isolated, isovolumically working guinea pig hearts (n=50), the release rate of adenosine and accumulation of
S
-adenosylhomocysteine (after 20 minutes of 200 μmol/L homocysteine), a measure of the free cytosolic adenosine concentration, were determined in the absence and presence of specific and powerful blockers of adenosine membrane transport (nitrobenzylthioinosine 1 μmol/L), adenosine deaminase (erythro-9-hydroxy-nonyl-adenine 5 μmol/L), and adenosine kinase (iodotubericidine 10 μmol/L). Data analysis with a distributed multicompartment model revealed a total cardiac adenosine production rate of 2294 pmol · min
−1
· g
−1
, of which 8% was produced in the extracellular region. Because of a high rate of intracellular metabolism, however, 70.3% of extracellularly produced adenosine was taken up into cellular regions, an effect that was effectively eliminated by membrane transport block. The resulting ≈2.8-fold increase of the interstitial adenosine concentration evoked near-maximal coronary dilation.
Conclusions
—We rejected the hypothesis that the cytosolic adenosine concentration exceeds the interstitial. Rather, there is significant extracellular production, and the parenchymal cell represents a sink, not a source, for adenosine under well-oxygenated conditions.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
99 articles.
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