Coronary response to diadenosine tetraphosphate after ischemia-reperfusion in the isolated rat heart

Diadenosine tetraphosphate (AP4A) is a vasoactive mediator that may be released from platelet granules and that may reach higher plasma concentrations during coronary ischemia-reperfusion. The objective of this study was to analyze its coronary effects in such conditions. To this, rat hearts were perfused in a Langendorff preparation and the coronary response to Ap4A (10− 7-10− 5 M) was recorded. In control hearts, Ap4A produced concentration-dependent vasodilatation both at the basal coronary resting tone and after precontracting coronary vasculature with 11-dideoxy-1a,9a-epoxymethanoprostaglandin F2α (U46619), and this vasodilatation was reduced by reactive blue 2 (2 × 10− 6 M), glibenclamide (10− 5 M), H89 (10− 6 M), U73122 (5 × 10− 6 M) and endothelin-1 (10− 9 M), but not by L-NAME (10− 4 M), isatin (10− 4 M), GF109203x (5 × 10− 7 M), or wortmannin (5 × 10− 7 M). After ischemia-reperfusion, the vasodilatation to Ap4A diminished, both in hearts with basal or increased vascular tone, and in this case the relaxation to Ap4A was not modified by reactive blue 2, L-NAME, glibenclamide, isatin, H89, GF109203x or wortmannin, although it was reduced by U73122 and endothelin-1. UTP produced coronary relaxation that was also reduced after ischemia-reperfusion. These results suggest that the coronary relaxation to Ap4A is reduced after ischemia-reperfusion, and that this reduction may be due to impaired effects of KATP channels and to reduced response of purinergic P2Y receptors.