Ikeda Y, Young L H, Scalia R, Lefer A M
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Methods Find Exp Clin Pharmacol. 2000 Sep;22(7):563-71.
The effects of L-citrulline, the byproduct of nitric oxide (NO) synthesis, and its stereoisomer D-citrulline were studied in a polymorphonuclear leukocyte (PMN)-dependent isolated perfused rat heart model consisting of 20 min of global ischemia and 45 min of reperfusion. Ischemic hearts reperfused with either D- or L-citrulline (20 nM) exhibited a marked preservation of left ventricular developed pressure and of maximal rate of development of left ventricular developed pressure, compared to hearts perfused without either D- or L-citrulline (both p < 0.001). In addition, both D- and L-citrulline significantly attenuated PMN accumulation in the post-reperfused myocardium from 288 +/- 33 PMNs/mm2 in untreated hearts to 89 +/- 10 and 76 +/- 6 PMNs/mm2, respectively (both p < 0.001). In isolated rat aortic rings, neither D- or L-citrulline induced any vasodilation or release of nitric oxide from the vascular endothelium. However, expression of P-selectin on the coronary vascular endothelium was markedly attenuated in hearts perfused with either D- or L-citrulline compared to ischemic-reperfused hearts without citrulline (both p < 0.001). These results provide evidence that D- or L-citrulline significantly attenuates PMN-induced cardiac contractile dysfunction in the isolated perfused rat heart subjected to ischemia/reperfusion via a non-NO-mediated mechanism.
在一个多形核白细胞（PMN）依赖的离体灌注大鼠心脏模型中，研究了一氧化氮（NO）合成的副产物L-瓜氨酸及其立体异构体D-瓜氨酸的作用，该模型包括20分钟的全心缺血和45分钟的再灌注。与未用D-或L-瓜氨酸灌注的心脏相比，用D-或L-瓜氨酸（20 nM）再灌注的缺血心脏左心室舒张末压和左心室舒张末压最大上升速率均得到显著保留（两者p < 0.001）。此外，D-和L-瓜氨酸均显著减轻了再灌注后心肌中PMN的积聚，从未经处理的心脏中的288±33个PMN/mm²分别降至89±10和76±6个PMN/mm²（两者p < 0.001）。在离体大鼠主动脉环中，D-或L-瓜氨酸均未诱导血管舒张或血管内皮释放一氧化氮。然而，与未用瓜氨酸进行缺血再灌注的心脏相比，用D-或L-瓜氨酸灌注的心脏中冠状血管内皮上P-选择素的表达明显减弱（两者p < 0.001）。这些结果提供了证据，表明D-或L-瓜氨酸通过非NO介导的机制，显著减轻了在离体灌注的缺血/再灌注大鼠心脏中PMN诱导的心脏收缩功能障碍。
