Mechanism of the production of reactive nitrogen species during renal ischemic-reperfusion insult

在循环中，一氧化氮(NO)以相对稳定的血红蛋白-NO加合物(HbNO)的形式存在，这意味着HbNO的含量可以反映血液中NO的浓度。已有报道使用电子顺磁共振(EPR)方法在人体血液中成功检测到HbNO信号。然而，要获得正常血液中良好的HbNO信号存在一定的困难。为了克服这些困难，我们引入了EPR信号减法。用此方法证实，静脉注射L精氨酸可提高戊巴比妥钠麻醉大鼠的HbNO浓度，但不能增加D-精氨酸的浓度。血管紧张素转换酶抑制剂替莫普利能改善L高血压大鼠的NO动力学异常。静脉注射NO_2后，大鼠左肾动脉结扎40分钟。左肾结扎松解5分钟后，取左、右肾组织和静脉血。用EPR法测定肾组织和静脉血中Hb^&lt；15&gt；NO浓度。左(缺血)肾组织中Hb^&lt；15&gt；NO浓度明显高于右(非缺血)肾组织。缺血再灌流大鼠静脉血中NO浓度明显高于AHAM手术非缺血大鼠。这些结果表明，NO_2没有生成途径，缺血-再灌注损伤可刺激NO_2的生成

In circulation, nitric oxide(NO) exists as relatively atable hemoglobin-NO adduct(HbNO), which means that the amount of HbNO may reflect the blood NO concentration. HbNO signal has been reported to be successfully detected in human blood using electron paramagnetic resonance(EPR) method. However, there were some difficulties to obtain a fine HbNO signal of nornal blood. We itroduced the EPR signal subtraction method to overcome the difficulties. Using this method, we confirmed that HbNO concentrarion in pentobarbital-anesthetized rats were augmented by infusion of L-arginine but not D-argimine. We also emenstrated that temocapril, an ACE inhibitor, improved abnormalities of NO dynamics in the L-MAME-induced hypertensive rats.After the intravebous infusion of ^<15>NO_2, the left renal artery of a rat was clumped for 40 minutes. Five minutes after the release of left renal occluaion, left and right renal tissues and venous blood were obtained. Hb^<15>NO concentration of renal tissues and venous blood was evaluated using EPR method. Hb^<15>NO concentrarion of left (ischemic) renal tissue is much higher than that of right(non-ischemic) renal tissue. Hb^<15>NO concentration of venous blood in ischemic-reperfused rat is much higher than that in aham operated non-ischemic rat. These results indicate that there is NO generation pathway from NO_2 and ischemic-reperfusion insult stimulates the NO generation from NO_2