Coronary artery reperfusion: The ADP receptor P2Y(1) mediates early reactive hyperemia in vivo in pigs

The physiological mechanisms that regulate reactive hyperemia are not fully understood. We postulated that the endothelial P2Y(1) receptor that release vasodilatory factors in response to ADP might play a vital role in the regulation of coronary flow. Intracoronary flow was measured with a Doppler flow-wire in a porcine model. 2-MeSADP (10(−5) M), ATP (10(−4) M) or UTP (10(−4) M) alone or as co-infusion with a selective P2Y(1) receptor blocker, MRS 2179 (10(−3) M) was locally delivered through the tip of a coronary angioplasty balloon. In separate pigs the coronary artery was occluded with the balloon for 10 min. During the first and tenth minutes of coronary ischemia, 2.5 ml of MRS 2179 (10(−3) M) was delivered distal to the occlusion in 8 pigs, 10 pigs were used as controls. MRS 2179 fully inhibited the 2-MeSADP-mediated coronary flow increase (P < 0.05) with no effect on UTP, indicating selective P2Y(1) inhibition. ATP-mediated flow increase was significantly inhibited by MRS 2179. During reactive hyperemia following coronary occlusion, flow increased by nearly sevenfold. MRS 2179, however, reduced the post-ischemic hyperemia by a mean of 46% during the period 1–2.5 min following balloon deflation (P < 0.05), which corresponds to peak velocity flow during reperfusion. In conclusion, MRS 2179, a selective P2Y(1) receptor blocker, significantly reduces the increased coronary flow caused both by 2-MeSADP and reactive hyperemia in coronary arteries. Thus, ADP acting on the endothelial P2Y(1) receptor may play a major role in coronary flow during post-ischemic hyperemia.