Moraru I I, Jones R M, Popescu L M, Engelman R M, Das D K
Department of Surgery, University of Connecticut School of Medicine, Farmington 06030-1110, USA.
Biochim Biophys Acta. 1995 Jul 20;1268(1):1-8. doi: 10.1016/0167-4889(95)00016-l.
The aim of this study was to establish whether or not alpha 1-adrenergic receptors are implicated in triggering phosphoinositide hydrolysis and intracellular Ca2+ accumulation during myocardial ischemia and reperfusion. In isolated perfused rat hearts, the selective alpha 1-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, alpha 1-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 alpha 1-adrenergic receptor-induced polyphosphoinositide hydrolysis.
本研究的目的是确定α1-肾上腺素能受体是否参与心肌缺血和再灌注期间磷酸肌醇水解及细胞内Ca2+蓄积的触发过程。在离体灌注大鼠心脏中，选择性α1-受体拮抗剂哌唑嗪可消除30分钟缺血后再灌注30分钟所诱导的细胞内肌醇磷酸放射性掺入增加，并选择性地阻断磷酸肌醇的降解；仅观察到缺血/再灌注诱导的其他磷脂类丢失有轻微变化。此外，在fura 2负载心脏的心外膜胞质游离Ca2+实时记录中，记录到哌唑嗪诱导的缺血/再灌注Ca2+超载减少。观察到早期缺血Ca2+升高受到抑制，以及胞质游离Ca2+峰值降低，且再灌注期间更快恢复至正常水平。此外，α1-肾上腺素能阻断导致再灌注期间心肌功能恢复显著改善：左心室舒张末压升高和收缩压最大上升速率分别与时间平均胞质Ca2+降低和Ca2+瞬变幅度增加平行。结论是，缺血和再灌注期间心肌Ca2+超载可能由α1-肾上腺素能受体诱导的多磷酸肌醇水解触发。
