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Adenosine concentration in the porcine coronary artery wall and A 2A receptor involvement in hypoxia‐induced vasodilatation
Author(s) -
Frøbert Ole,
Haink Gesine,
Simonsen Ulf,
Gravholt Claus H.,
Levin Max,
Deussen Andreas
Publication year - 2006
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2005.100115
Subject(s) - adenosine , microdialysis , vasodilation , myograph , medicine , adenosine receptor , hypoxia (environmental) , chemistry , endocrinology , interstitial fluid , adenosine deaminase , extracellular , receptor , oxygen , biochemistry , agonist , organic chemistry
We tested whether hypoxia‐induced coronary artery dilatation could be mediated by an increase in adenosine concentration within the coronary artery wall or by an increase in adenosine sensitivity. Porcine left anterior descendent coronary arteries, precontracted with prostaglandin F 2α (10 −5 m ), were mounted in a pressure myograph and microdialysis catheters were inserted into the tunica media. Dialysate adenosine concentrations were analysed by HPLC. Glucose, lactate and pyruvate were measured by an automated spectrophotometric kinetic enzymatic analyser. The exchange fraction of [ 14 C]adenosine over the microdialysis membrane increased from 0.32 ± 0.02 to 0.46 ± 0.02 ( n = 4, P < 0.01) during the study period. At baseline, interstitial adenosine was in the region of 10 n m which is significantly less than previously found myocardial concentrations. Hypoxia ( P O 230 mmHg for 60 min, n = 5) increased coronary diameters by 20.0 ± 2.6% ( versus continuous oxygenation −3.1 ± 2.4%, n = 6, P < 0.001) but interstitial adenosine concentration fell. Blockade of adenosine deaminase (with erythro‐9‐(2‐hydroxy‐3‐nonyl‐)‐adenine, 5 μ m ), adenosine kinase (with iodotubericidine, 10 μ m ) and adenosine transport (with n ‐nitrobenzylthioinosine, 1 μ m ) increased interstitial adenosine but the increase was unrelated to hypoxia or diameter. A coronary dilatation similar to that during hypoxia could be obtained with 30 μ m of adenosine in the organ bath and the resulting interstitial adenosine concentrations ( n = 5) were 20 times higher than the adenosine concentration measured during hypoxia. Adenosine concentration–response experiments showed vasodilatation to be more pronounced during hypoxia ( n = 9) than during normoxia ( n = 9, P < 0.001) and the A 2A receptor antagonist ZM241385 (20 n m , n = 5), attenuated hypoxia‐induced vasodilatation while the selective A 2B receptor antagonist MRS1754 (20 n m , n = 4), had no effect. The lactate/pyruvate ratio was significantly increased in hypoxic arteries but did not correlate with adenosine concentration. We conclude that hypoxia‐induced coronary artery dilatation is not mediated by increased adenosine produced within the artery wall but might be facilitated by increased adenosine sensitivity at the A 2A receptor level.