Department of Cardiology, Lund University, Lund, Sweden.
Purinergic Signal. 2004 Dec;1(1):59-65. doi: 10.1007/s11302-004-4742-7.
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.
调节反应性充血的生理机制尚未完全阐明。我们推测，ADP 反应性释放血管舒张因子的内皮 P2Y(1) 受体可能在冠状动脉血流调节中发挥重要作用。在猪模型中，使用多普勒血流导丝测量冠状动脉内血流。单独或与 P2Y(1) 受体选择性阻滞剂 MRS 2179（10(-3) M）共同输注 2-MeSADP（10(-5) M）、ATP（10(-4) M）或 UTP（10(-4) M），通过冠状动脉成形术球囊尖端局部给药。在单独的猪中，用球囊将冠状动脉闭塞 10 分钟。在冠状动脉缺血的第一和第十分钟，在 8 只猪中于闭塞远端给予 2.5ml MRS 2179（10(-3) M），10 只猪作为对照。MRS 2179 完全抑制 2-MeSADP 介导的冠状动脉血流增加（P<0.05），对 UTP 无影响，表明选择性 P2Y(1) 抑制。MRS 2179 显著抑制 ATP 介导的血流增加。在冠状动脉闭塞后的反应性充血期间，血流增加近七倍。然而，MRS 2179 在球囊放气后 1-2.5 分钟期间平均减少了缺血后再充血 46%（P<0.05），这与再灌注期间的峰值速度血流相对应。总之，选择性 P2Y(1) 受体阻滞剂 MRS 2179 显著减少 2-MeSADP 和冠状动脉反应性充血引起的冠状动脉血流增加。因此，ADP 作用于内皮 P2Y(1) 受体可能在缺血后再充血期间的冠状动脉血流中起主要作用。
