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 1,000 μmol/L) was superfused onto the heart surface before and during the superfusion of 10 μmol/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 10 μmol/L of 8-PT. In addition to 8-PT, 30 μmol/L of pyridoxalphosphate-6-azophenyl 2',4'-disulphonic acid (PPADS), a P(2X) purinoceptor blocker in Protocol 3, or 300 μmol/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, 10 μmol/L of α,β-methylene ATP, an agonist of P(2X) 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 ≤150 μm: 24.5±2.2% vs large vessel >150 μm: 10.6±1.5% at a dose of 1,000 μmol/L, p<0.001). On the other hand, intraluminally applied AP4A also dilated arterioles, but no size dependency was shown. In the presence of 8-PT, vasodilatory responses to superfused and intraluminally applied AP4A were attenuated and the lower doses of AP4A constricted arterioles. This vasoconstrictor effect was not affected by PPADS. The vasodilatory effect of the higher doses of AP4A was almost abolished in the presence of LNNA. α, β-methylene ATP had no effect on coronary microvascular diameters. AP4A has bidirectional effects on coronary arterial microvessels: vasodilatory effects mediated by P1 purinoceptors and NO, which might be mediated by P(2Y) purinoceptors, and a vasoconstrictor effect, which is not mediated by P(2X) purinoceptors.
- Canine heart
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine