Coronary response to diadenosine triphosphate after ischemia-reperfusion in the isolated rat heart.
Diadenosine triphosphate (Ap3A) is a vasoactive mediator stored in platelet granules that may be released during coronary ischemia-reperfusion. To study its coronary effects in such circumstances, rat hearts were perfused in a Langendorff preparation and the coronary response to Ap3A (10(-7)-10(-5) mol/L) was recorded. Both at basal coronary resting tone and after precontraction with 11-dideoxy-1a,9a-epoxymethanoprostaglandin F(2)(α) (U46619), Ap3A produced concentration-dependent vasodilation in the heart, which was attenuated following ischemia-reperfusion. Ap3A-induced relaxation was also attenuated in control conditions and after ischemia-reperfusion by the purinergic P2Y antagonist reactive blue 2 (2 × 10(-6) mol/L), the P2Y(1) antagonist MRS 2179 (10(-5) mol/L), the nitric oxide synthesis inhibitor N-omega-nitro-l-arginine methyl ester (l-NAME; 10(-4) mol/L) and the ATP-dependent potassium channel blocker glibenclamide (10(-5) mol/L). These results suggest that Ap3A induces coronary vasodilation, an effect attenuated by ischemia-reperfusion due to the functional impairment of purinergic P2Y receptors and K(ATP) channels, and/or reduced nitric oxide release. This impairment of vasodilation may contribute to the coronary dysregulation that occurs during ischemia-reperfusion.
Departamento de Fisiología, Universidad Autónoma de Madrid, Madrid, Spain. angeluis.villalon@uam.es
Angel Luis
AL
García-Villalón
Nuria
N
Fernández
Luis
L
Monge
Miriam
M
Granado
Gonzalo
G
Carreño-Tarragona
Juan Carlos
JC
Figueras
Godofredo
G
Diéguez
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D015226:Dinucleoside Phosphates / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology*; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D014664:Vasodilation; D014665:Vasodilator Agents / Q000378:metabolism*
D015226:Dinucleoside Phosphates; D014665:Vasodilator Agents; C011440:diadenosine triphosphate