Inserm, EA4173 ERI 22, Agression vasculaire et réponses tissulaires, UCBLyon1, 69008 Lyon, France.
Nitric Oxide. 2010 Nov 1;23(3):194-8. doi: 10.1016/j.niox.2010.06.002. Epub 2010 Jun 12.
An overwhelming nitric oxide (NO) production is a crucial step in the circulatory events as well as in the cellular alterations taking place in septic shock. However, evidences of this role arise from studies assessing the NO production on an intermittent basis precluding any clear evaluation of temporal relationship between NO production and circulatory alterations. We evaluated this relationship by using a NO specific electrode allowing a continuous measurement of NO production. Septic shock was induced by a cecal ligation and puncture (CLP) in a first group of anesthetized rats. After the same CLP, a second group received a selective iNOS inhibitor (L-NIL). Control rats were sham operated or sham operated with L-NIL administration. While NO concentration was measured every 2 min by a NO-sensitive electrode over 7h following CLP, the liver microcirculation was recorded by a laser-Doppler flowmeter. CLP induced a severe septic shock with hypotension occurring at a mean time of 240 min after CLP. At the same time, an increase in liver NO concentration was observed, whereas a decrease in microvascular liver perfusion was noted. In the septic shock group, L-NIL administration induced an increase in arterial pressure whereas the liver NO concentration returned to baseline values. In addition, shock groups experienced an increase in iNOS mRNA. These data showed a close temporal relationship between the increase in liver NO concentration and the microvascular alteration taking place in the early period of septic shock induced by CLP. The iNOS isoform is involved in this NO increase.
大量一氧化氮（NO）的产生是循环事件以及发生在感染性休克中的细胞改变的关键步骤。然而，这些作用的证据来自于评估间歇性NO 产生的研究，这排除了对 NO 产生与循环改变之间的时间关系的任何明确评估。我们通过使用允许连续测量 NO 产生的特定 NO 电极来评估这种关系。在第一组麻醉大鼠中通过盲肠结扎和穿刺（CLP）诱导感染性休克。在相同的 CLP 后，第二组接受选择性 iNOS 抑制剂（L-NIL）治疗。对照大鼠接受假手术或假手术加 L-NIL 给药。在 CLP 后 7 小时内，通过 NO 敏感电极每 2 分钟测量一次 NO 浓度，同时通过激光多普勒流量计记录肝微循环。CLP 导致严重的感染性休克，低血压发生在 CLP 后平均 240 分钟。同时，观察到肝 NO 浓度增加，而肝微血管灌注减少。在感染性休克组中，L-NIL 给药诱导动脉压升高，而肝 NO 浓度恢复到基线值。此外，休克组 iNOS mRNA 增加。这些数据表明，在 CLP 诱导的感染性休克早期，肝 NO 浓度的增加与微血管改变之间存在密切的时间关系。iNOS 同工型参与了这种 NO 的增加。
