Differential Coronary Microvascular Exchange Responses to Adenosine: Roles of Receptor and Microvessel Subtypes

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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 venulePsPSA(10.7 ± 4.8× 10−7cm · s−1) was greater than that of arterioles (6.4± 2.8× 10−7cm · s−1;p< .05). ArteriolarPsPSAdecreased (p< .05) with adenosine suffusion over the range from 10−8to 10−5M, while venularPsPSAdid not change. The nonselective A1and A2receptor antagonist, 8‐(p‐sulfophenyl) theophylline, blocked the adenosine‐induced decrease in arteriolarPsPSA. Messenger RNA for adenosine A1, A2A, A2B, and A3receptors 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:ArteriolarPsPSAdecreases with adenosine suffusion but not venularPsPSA. Adenosine A1, A2A, and A2Breceptors are expressed in both arterioles and venules. Selective receptor‐linked cellular signaling mechanisms underlying the regulation of permeability remain to be determined.