Coronary response to diadenosine triphosphate after ischemia–reperfusion in the isolated rat heart

Abstract

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 F2 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 P2Y1 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 KATP channels, and/or reduced nitric oxide release. This impairment of vasodilation may contribute to the coronary dysregulation that occurs during ischemia–reperfusion.