Abstract
Objective: To assess the role of adenosine receptors in the regulation of coronary microvascular permeability to porcine serum albumin (PsPSA).
Methods: Solute flux was measured in single perfused arterioles and venules isolated from pig hearts using fluorescent dye-labeled probes by microspectro-fluorometry. Messenger RNA, protein, and cellular distribution of adenosine receptors in arterioles and venules were analyzed by RT-PCR, immunoblot, and immunofluorescence.
Results: Control venule PsPSA (10.7 ± 4.8× 10− 7 cm · s− 1) was greater than that of arterioles (6.4± 2.8× 10−7 cm · s−1; p < .05). Arteriolar PsPSA decreased (p < .05) with adenosine suffusion over the range from 10− 8 to 10−5 M, while venular PsPSA did not change. The nonselective A1 and A2 receptor antagonist, 8-(p-sulfophenyl) theophylline, blocked the adenosine-induced decrease in arteriolar PsPSA. Messenger RNA for adenosine A1, A2A, A2B, and A3 receptors was expressed in arterioles and venules. Protein for A1, A2A, and A2B, but not A3, was detected in both microvessel types and was further demonstrated on vascular endothelial cells.
Conclusion: Arteriolar PsPSA decreases with adenosine suffusion but not venular PsPSA. Adenosine A1, A2A, and A2B receptors are expressed in both arterioles and venules. Selective receptor-linked cellular signaling mechanisms underlying the regulation of permeability remain to be determined.
Microcirculation (2005) 12, 313–326. doi:10.1080/10739680590934736
Supported by NIH grant PO1 HL 52490 and NASA grant NAG 5-12300. The authors would like to thank Donna A. Williams for her permission to include some unpublished permeability data generated during her tenure in the laboratory. We also are grateful for Liping Ji, Susan Bingaman, and Steven W. Sieveking's expert technical assistance.