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This Article Full Text Full Text (PDF) All Versions of this Article: 570/2/375    most recent jphysiol.2005.100115v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Frøbert, O. Articles by Deussen, A. Search for Related Content PubMed PubMed Citation Articles by Frøbert, O. Articles by Deussen, A. Related Collections Cardiovascular

¹ Department of Cardiology, Center for Cardiovascular Research, Aalborg Hospital, Aarhus University Hospital, Denmark
² Department of Pharmacology, University of Aarhus, Denmark
³ Institute of Physiology, Medical Faculty Carl Gustav Carus, Technical University Dresden, Germany
⁴ Department of Endocrinology M, Aarhus Sygehus, Aarhus University Hospital, Denmark
⁵ Wallenberg Laboratory, Sahlgrenska University Hospital, Göteborg, Sweden

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 F₂ (10^–5M), 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 [¹⁴C]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 nM which is significantly less than previously found myocardial concentrations. Hypoxia (P_O2 30 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 µM), adenosine kinase (with iodotubericidine, 10 µM) and adenosine transport (with n-nitrobenzylthioinosine, 1 µM) 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 µM 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 nM, n= 5), attenuated hypoxia-induced vasodilatation while the selective A_2B receptor antagonist MRS1754 (20 nM, 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.

(Received 17 October 2005; accepted after revision 10 November 2005; first published online 10 November 2005)
Corresponding author O. Frøbert: Department of Cardiology, Center for Cardiovascular Research, Aalborg Hospital, Aarhus University Hospital, DK-9000 Aalborg, Denmark. Email: frobert{at}dadlnet.dk

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