Differential coronary microvascular exchange responses to adenosine: roles of receptor and microvessel subtypes.

Objective: To assess the role of adenosine receptors in the regulation of coronary microvascular permeability to porcine serum albumin (P(s)(PSA)).

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 P(s)(PSA) (10.7 +/- 4.8 x 10(- 7) cm x s(- 1)) was greater than that of arterioles (6.4+/- 2.8 x 10(-7) cm . s(-1); p < .05). Arteriolar P(s)(PSA) decreased (p < .05) with adenosine suffusion over the range from 10(- 8) to 10(-5) M, while venular P(s)(PSA) did not change. The nonselective A(1) and A(2) receptor antagonist, 8-(p-sulfophenyl) theophylline, blocked the adenosine-induced decrease in arteriolar P(s)(PSA). Messenger RNA for adenosine A(1), A(2A), A(2B), and A(3) receptors was expressed in arterioles and venules. Protein for A(1), A(2A), and A(2B), but not A(3), was detected in both microvessel types and was further demonstrated on vascular endothelial cells.

Conclusion: Arteriolar P(s)(PSA) decreases with adenosine suffusion but not venular P(s)(PSA). Adenosine A(1), A(2A), and A(2B) receptors are expressed in both arterioles and venules. Selective receptor-linked cellular signaling mechanisms underlying the regulation of permeability remain to be determined.