Contribution of Adenosine A2A and A2B Receptors to Ischemic Coronary Dilation: Role of KV and KATP Channels
Contribution of Adenosine A2A and A2B Receptors to Ischemic Coronary Dilation: Role of KV and KATP Channels
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DOI：
10.1111/j.1549-8719.2010.00054.x
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发表时间：
2010-01-01
期刊：
影响因子：
2.4
通讯作者：
Tune, Johnathan D.
中科院分区：
文献类型：
--
作者：
Berwick, Zachary C.;Payne, Gregory A.;Tune, Johnathan D.
本研究旨在阐明腺苷 A(2A) 和 A(2B) 受体对冠状动脉反应性充血和下游 K+ 通道的影响。在开胸麻醉狗中测量冠状动脉血流量。在对照条件下，腺苷剂量依赖性地将冠状动脉流量从 0.72 +/- 0.1 增加到 2.6 +/- 0.5 mL/min/g。用 SCH58261 (1 μm) 抑制 A(2A) 受体可将腺苷诱导的扩张减弱约 50%，而与 A(2B) 受体拮抗剂咯嗪 (3 μm) 联合给药则不会产生额外效果。 SCH58261 显着减少了短暂 15 秒闭塞引起的反应性充血；债务/偿还比率从 343 +/- 63 下降至 232 +/- 44%。单独使用咯嗪可将腺苷引起的冠状动脉血流量增加减弱约 30%，但未能改变反应性充血。 A(2A) 受体激动剂 CGS21680（10 μg 推注）使冠状动脉血流量增加 3.08 +/- 0.31 mL/min/g。通过用 4-氨基吡啶 (0.3 mm) 抑制 K-V 通道，该扩张器反应减弱至 0.76 +/- 0.14 mL/分钟/g，通过用格列本脲 (3 mg/kg) 抑制 K-ATP 通道，该扩张器反应减弱至 0.11 +/- 0.31 mL/分钟/g。联合给药消除了 CGS21680 的血管舒张作用。这些数据表明，A(2A) 受体通过激活 K-V 和 K-ATP 通道，有助于冠状动脉舒张，以响应心脏缺血。
This study was designed to elucidate the contribution of adenosine A(2A) and A(2B) receptors to coronary reactive hyperemia and downstream K+ channels involved. Coronary blood flow was measured in open-chest anesthetized dogs. Adenosine dose-dependently increased coronary flow from 0.72 +/- 0.1 to 2.6 +/- 0.5 mL/minute/g under control conditions. Inhibition of A(2A) receptors with SCH58261 (1 mu m) attenuated adenosine-induced dilation by similar to 50%, while combined administration with the A(2B) receptor antagonist alloxazine (3 mu m) produced no additional effect. SCH58261 significantly reduced reactive hyperemia in response to a transient 15 second occlusion; debt/repayment ratio decreased from 343 +/- 63 to 232 +/- 44%. Alloxazine alone attenuated adenosine-induced increases in coronary blood flow by similar to 30% but failed to alter reactive hyperemia. A(2A) receptor agonist CGS21680 (10 mu g bolus) increased coronary blood flow by 3.08 +/- 0.31 mL/minute/g. This dilator response was attenuated to 0.76 +/- 0.14 mL/minute/g by inhibition of K-V channels with 4-aminopyridine (0.3 mm) and to 0.11 +/- 0.31 mL/minute/g by inhibition of K-ATP channels with glibenclamide (3 mg/kg). Combined administration abolished vasodilation to CGS21680. These data indicate that A(2A) receptors contribute to coronary vasodilation in response to cardiac ischemia via activation of K-V and K-ATP channels.