title: Diadenosine polyphosphates are selective vasoconstrictors in human coronary artery bypass grafts.
abstract: 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 vasoconstrictor 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 alphabetamethyleneATP-sensitive receptor. Responses to both Ap(5)A and alphabetamethyleneATP were inhibited by suramin but were insensitive to the P2X(1) 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 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.
authors.affiliation: The Cardiothoracic Centre, Liverpool NHS Trust, Thomas Drive, Liverpool L14 3PE, UK. conant@liv.ac.uk
authors.forename: Alan R
authors.initials: AR
authors.lastname: Conant
authors.forename: Thomas
authors.initials: T
authors.lastname: Theologou
authors.forename: Walid C
authors.initials: WC
authors.lastname: Dihmis
authors.forename: Alec W M
authors.initials: AW
authors.lastname: Simpson
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D001026:Coronary Artery Bypass; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008323:Mammary Arteries / Q000637:transplantation; D008875:Middle Aged; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D017534:Radial Artery / Q000637:transplantation; D018047:Receptors, Purinergic P1 / Q000187:drug effects; D012501:Saphenous Vein / Q000637:transplantation; D014662:Vasoconstrictor Agents; D014667:Vasopressins / Q000494:pharmacology
chemical_list: D015226:Dinucleoside Phosphates; D018047:Receptors, Purinergic P1; D014662:Vasoconstrictor Agents; D014667:Vasopressins; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; C012275:P(1),P(5)-di(adenosine-5'-)pentaphosphate; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate