Diadenosine polyphosphates are selective vasoconstrictors in human coronary artery bypass grafts

Diadenosine polyphosphates (Ap(n)A) are released by degranulating platelets and high, local concentrations may form at sites of platelet activation. Radial artery grafts, now often used alongside the internal mammary artery in coronary artery bypass surgery, are particularly reactive to several vasoconstrictors but the response to Ap(n)A has not been investigated. This study compared the vasoconsttictor activity of Ap(n)A in human radial artery with other vessels commonly used as bypass grafts. Radial artery demonstrated robust concentration-dependent vasoconstriction to Ap(n)A (n=4-6) at concentrations in the micromolar range. In contrast, average responses in internal mammary artery were negligible. Cross-desensitization revealed that Ap(n)A-mediated vasoconstriction occurred via an alpha beta methyleneATP-sensitive receptor. Responses to both Ap(5)A and alpha beta methyleneATP were inhibited by suramin but were insensitive to the P2X(1) receptor antagonist 8,8'-[Carbonylbis(imino4,1-phenylenecarbonylimino-4, 1-phenylenecarbonylimino)] bis-1,3,5-naphthalenctrisulfonic acid (NF279). Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) enhanced responses to Ap(5)A. Similar responses were obtained in saphenous vein. In conclusion, diadenosine polyphosphates contract radial artery and saphenous vein by an as yet uncharacterized P2X receptor but have only limited activity in internal mammary artery. The selective activity of diadenosine polyphosphates in radial artery would implicate them as potential mediators of post-operative contraction in this graft. (C) 2008 Elsevier Inc. All rights reserved.