Effects of dinucleoside polyphosphates on regulation of coronary vascular tone.
The aim of the present study was to investigate the effects of Xp(5)X and Xp(6)X (X = guanosine (G) or adenosine (A); n = 5 and 6), which have been identified in human platelets, on coronary vascular tone. The activation of purinoceptors in rat coronary vasculature by Xp(5)X and Xp(6)X was evaluated by measuring their effects on perfusion pressure in the Langendorff perfused rat. Ap(5)X and Ap(6)X induced dose-dependent vasodilation that was due to P2Y(1) receptor activation, as evidenced by use of the selective P2Y(1) receptor antagonist 2'-deoxy-N(6)-methyl-adenosine 3',5'-diphosphate diammonium (MRS2179). Vasodilation was induced by NO release, as evidenced by inhibition of nitric oxide synthases (NO synthases) by N(G)-nitro-L-arginine methyl ester (L-NAME). The dose-dependent decrease in coronary perfusion pressure induced by Ap(5)X and Ap(6)X was converted to a dose-dependent increase in perfusion pressure after inhibition of NO synthases by L-NAME. After endothelium removal, the vasodilation elicited by Ap(5)X and Ap(6)X was converted to a vasoconstriction which could be inhibited by P2X receptor blockade. Ap(5)A, Ap(5)G, Ap(6)A and Ap(6)G are vasodilating or vasoconstricting nucleotides that activate P2Y(1) or P2X receptors depending on the status of the coronary vascular endothelium.
van der Giet
Markus
M
Medizinische Klinik IV, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin, Germany. vdGiet@zedat.fu-berlin.de
Schmidt
Sven
S
Tölle
Markus
M
Jankowski
Joachim
J
Schlüter
Hartmut
H
Zidek
Walter
W
Tepel
Martin
M
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D058913:Purinergic Agonists; D051381:Rats; D017208:Rats, Wistar; D011983:Receptors, Purinergic / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D015226:Dinucleoside Phosphates; D058913:Purinergic Agonists; D011983:Receptors, Purinergic