Diadenosine polyphosphates are selective vasoconstrictors in human coronary artery bypass grafts

Diadenosine polyphosphates (ApnA) 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 ApnA has not been investigated. This study compared the vasoconstrictor activity of ApnA in human radial artery with other vessels commonly used as bypass grafts. Radial artery demonstrated robust concentration-dependent vasoconstriction to ApnA (n=4–6) at concentrations in the micromolar range. In contrast, average responses in internal mammary artery were negligible. Cross-desensitization revealed that ApnA-mediated vasoconstriction occurred via an αβmethyleneATP-sensitive receptor. Responses to both Ap5A and αβmethyleneATP were inhibited by suramin but were insensitive to the P2X1 receptor antagonist 8,8′-[Carbonylbis(imino-4,1-phenylenecarbonylimino-4,1-phenylenecarbonylimino)]bis-1,3,5-naphthalenetrisulfonic acid (NF279). Pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS) enhanced responses to Ap5A. 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.