Prazosin reduces myocardial ischemia/reperfusion-induced Ca2+ overloading in rat heart by inhibiting phosphoinositide signaling.
Prazosin reduces myocardial ischemia/reperfusion-induced Ca2+ overloading in rat heart by inhibiting phosphoinositide signaling.
复制标题
Prazosin 通过抑制磷酸肌醇信号传导来减少大鼠心脏中心肌缺血/再灌注引起的 Ca2 超载。
DOI：
10.1016/0167-4889(95)00016-l
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Das,DK
中科院分区：
文献类型：
--
作者：
Moraru,II;Jones,RM;Popescu,LM;Engelman,RM;Das,DK
本研究的目的是确定在心肌缺血和再灌注过程中，α1-肾上腺素能受体是否参与触发磷酸肌醇水解和细胞内Ca 2+蓄积。在离体灌流大鼠心脏中，选择性α1受体拮抗剂哌唑嗪消除了30分钟缺血再灌注30分钟诱导的细胞肌醇磷酸放射性掺入的增加，并选择性地阻断磷酸肌醇的降解;仅观察到缺血/再灌注诱导的其他类别磷脂损失的微小变化。此外，哌唑嗪诱导的缺血/再灌注Ca 2+超载的减少记录在心外膜胞浆游离Ca 2+的实时记录在呋喃2负载的心脏。观察到早期缺血性Ca 2+升高的抑制，以及细胞溶质游离Ca 2+的较低峰值和再灌注期间更快地逆转至正常值。此外，α1-肾上腺素能受体阻滞剂可显著改善再灌注期间心肌功能的恢复：左室发展压和收缩压最大上升速率的增加分别与时间平均胞浆Ca ~（2+）的降低和Ca ~（2+）瞬变幅度的增加相一致。结论：缺血和再灌注期间心肌钙超载可能是由α1肾上腺素能受体诱导的聚磷酸肌醇水解引发的。
The aim of this study was to establish whether or not α1-adrenergic receptors are implicated in triggering phosphoinositide hydrolysis and intracellular Ca2+accumulation during myocardial ischemia and reperfusion. In isolated perfused rat hearts, the selective α1-receptor antagonist prazosin abolished the increase in radioactivity incorporation into cellular inositol phosphates induced by 30 min ischemia followed by 30 min reperfusion, and selectively blocked the degradation of phosphoinositides; only minor changes in the ischemia/reperfusion-induced loss of other classes of phospholipids were seen. In addition, a prazosin-induced decrease of ischemia/reperfusion Ca2+overloading was documented in real-time recordings of epicardial cytosolic free Ca2+in fura 2-loaded hearts. An inhibition of early ischemic Ca2+rise was observed, as well as a lower peak of cytosolic free Ca2+and a more rapid reversal to normal values during reperfusion. Moreover, α1-adrenergic blockade resulted in a significant improvement in the recovery of myocardial function during reperfusion: an increased left ventricular developed pressure and maximum rate of rise of systolic pressure paralleled the decrease in time-averaged cytosolic Ca2+and the increase in amplitude of Ca2+transients, respectively. It is concluded that myocardial Ca2+overloading during ischemia and reperfusion may be triggered by α1-adrenergic receptor-induced polyphosphoinositide hydrolysis.