Effect of Diadenosine Tetraphosphate(AP4A) on Coronary Arterial Microvessels in the Beating Canine Heart

Diadenosine tetraphosphate (AP4A) can be released from activated platelets and the present study examined its effect on coronary arterial microvessels. The role of purinoceptors in the coronary microcirculation in vivo was also investigated. In open chest dogs, coronary arterioles were observed using a microscope with a floating objective. In Protocol 1, AP4A (1, 10, 100 and 1, 000μmol/L) was superfused onto the heart surface before and during the superfusion of 10μmol/L of 8-phenyltheophylline (8-PT), a P1 purinoceptor blocker. In Protocol 2, AP4A (0.1, 1, 10, and 100 nmol·kg-1·min-1) was infused into the left anterior descending coronary artery before and during the superfusion of 10μmol/L of 8-PT. In addition to 8-PT, 30μmol/L of pyridoxalphosphate-6-azophenyl 2′, 4′-disulphonic acid (PPADS), a P2X purinoceptor blocker in Protocol 3, or 300μmol/L of Nω-nitro-L-arginine (LNNA) in Protocol 4, was continuously superfused, and 4 doses of AP4A were cumulatively superfused as in Protocol 1. In Protocol 5, 10μmol/L of α, β-methylene ATP, an agonist of P2X purinoceptors, was superfused for 60 min. Superfused AP4A dilated arterioles in a dose-dependent manner. The magnitude of dilatation was greater in smaller arterioles (small vessel ≤150μm: 24.5±2.2% vs large vessel > 150μm: 10.6±1.5% at a dose of 1, 000 μmol/L, p