Yang B C, Mehta J L
Department of Medicine, College of Medicine, University of Florida and the Veterans Affairs Medical Center, Gainesville 32610, USA.
Life Sci. 1997;61(3):229-36. doi: 10.1016/s0024-3205(97)00378-0.
To examine if inhibition of nitric oxide (NO) synthesis influences myocardial ischemia-reperfusion injury, male Sprague Dawley rats were administered the NO synthesis inhibitor N -nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, i.p.) or saline 6 hours prior to excising the heart and aorta. Aortic ring contractile response to norepinephrine (NE) was more pronounced and relaxation in response to acetylcholine was abolished in L-NAME-treated group (P<0.05 vs. saline-treated group), indicating inhibition of NO synthesis in the vascular tissues. In the isolated perfused Langendorff hearts, force of cardiac contraction (FCC) and coronary perfusion pressure (CPP) were higher and coronary flow was lower in the L-NAME-treated group, again suggesting inhibition of NO synthesis. Global ischemia (40 min) followed by reperfusion (30 min) resulted in a decrease in FCC and coronary flow and an increase in CPP in all hearts. Myocardial CK also decreased similarly in all hearts. However, ischemia-reperfusion-induced decline in myocardial superoxide dismutase (SOD) activity and increase in malondialdehyde were prevented in the L-NAME-treated group (P<0.01 vs. saline-treated hearts). Thus treatment with L-NAME with resultant inhibition of NO synthesis does not affect ischemia-reperfusion-induced cardiac dysfunction and injury in the isolated rat hearts, although the reduction in SOD activity and the rise in lipid peroxidation following reperfusion are attenuated.
为研究一氧化氮（NO）合成抑制是否影响心肌缺血再灌注损伤，在切除心脏和主动脉前6小时，给雄性Sprague Dawley大鼠腹腔注射NO合成抑制剂N-硝基-L-精氨酸甲酯（L-NAME，10 mg/kg）或生理盐水。L-NAME处理组中，主动脉环对去甲肾上腺素（NE）的收缩反应更明显，对乙酰胆碱的舒张反应消失（与生理盐水处理组相比，P<0.05），表明血管组织中NO合成受到抑制。在离体灌注的Langendorff心脏中，L-NAME处理组的心脏收缩力（FCC）和冠状动脉灌注压（CPP）较高，冠状动脉血流量较低，再次提示NO合成受到抑制。所有心脏在经历40分钟全心缺血后再灌注30分钟，均导致FCC和冠状动脉血流量下降，CPP升高。所有心脏中的心肌肌酸激酶（CK）也出现类似下降。然而，L-NAME处理组可防止缺血再灌注引起的心肌超氧化物歧化酶（SOD）活性下降和丙二醛增加（与生理盐水处理的心脏相比，P<0.01）。因此，L-NAME处理导致NO合成受抑制，虽可减轻再灌注后SOD活性降低和脂质过氧化增加，但不影响离体大鼠心脏缺血再灌注诱导的心脏功能障碍和损伤。
