ADENOSINE-A1 RECEPTOR MEDIATED PROTECTION OF THE GLOBALLY ISCHEMIC ISOLATED RAT-HEART
ADENOSINE-A1 RECEPTOR MEDIATED PROTECTION OF THE GLOBALLY ISCHEMIC ISOLATED RAT-HEART
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DOI：
10.1016/0022-2828(90)90970-d
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发表时间：
1990-01-01
影响因子：
5
通讯作者：
MENTZER, RM
中科院分区：
文献类型：
--
作者：
LASLEY, RD;RHEE, JW;MENTZER, RM
本研究的目的是确定腺苷对缺血心肌的心脏保护作用是否通过与特定腺苷受体亚型的相互作用介导。将以恒定流量灌注的离体大鼠心脏置于整体常温（37 ℃）下。C）缺血，缺血性挛缩发作时间（TOIC）用作心肌缺血性损伤的标志物。用腺苷和R-苯基异丙基腺苷（PIA）（一种腺苷A1受体激动剂）处理的心脏显示出比对照心脏显著更大的TOIC（18.60 ± 0.01）。0.40和16.64 .+-。1.15 min，分别为9.12 ±. 0.66 min），而腺苷A2受体激动剂苯氨基腺苷对TOIC没有影响（11.73 ± 0.05）。0.87 min）。BW A1433 U，一种腺苷受体拮抗剂，阻断腺苷和PIA对缺血性挛缩时间的影响，BW A1433 U没有改变硝苯地平或普萘洛尔延迟缺血性挛缩发作的能力，从而表明这种化合物对腺苷受体的特异性。与对照心脏相比，PIA治疗的心脏在整个缺血期表现出显著更高的ATP水平，而BW A1433 U治疗的心脏显示ATP含量迅速下降。这些结果表明，腺苷对缺血心肌的有益作用是通过与腺苷A1受体的相互作用介导的，并且内源性形成的腺苷在减轻心肌缺血性损伤中起作用。
The purpose of this study was to determine if the cardioprotective effect of adenosine on the ischemic myocardium is mediated by interaction with specific adenosine receptor subtypes. Isolated rat hearts perfused at constant flow were subjected to global normothermic (37.degree. C) ischemia and the time to onset of ischemic contracture (TOIC) was used as a marker of myocardial ischemic injury. Hearts treated with adenosine and R-phenylisopropyladenosine (PIA), an adenosine A1 receptor agonist, exhibited a significantly greater TOIC than control hearts (18.60 .+-. 0.40 and 16.64 .+-. 1.15 min, respectively vs 9.12 .+-. 0.66 min), whereas phenylaminoadenosine, an adenosine A2 receptor agonist, had no effect on TOIC (11.73 .+-. 0.87 min). BW A1433U, an adenosine receptor antagonist, blocked the effects of adenosine and PIA on ischemic contracture time, and BW A1433U did not alter the ability of nifedipine or propranolol to delay the onset of ischemic contracture, thus indicating the specificity of this compound for the adenosine receptor. PIA-treated hearts exhibited significantly greater ATP levels throughout the ischemic period compared to control hearts, whereas hearts treated with BW A1433U showed a rapid decline in ATP content. These results suggest that the beneficial effects of adenosine on the ischemic myocardium are mediated by interaction with adenosine A1 receptors, and that endogenously formed adenosine plays a role in attenuating myocardial ischemic damage.