Stoclet J C, Martínez M C, Ohlmann P, Chasserot S, Schott C, Kleschyov A L, Schneider F, Andriantsitohaina R
Laboratoire de Pharmacologie et Physiologie Cellulaires, CNRS ERS 653, Faculté de Pharmacie, Illkirch, France.
Circulation. 1999 Jul 13;100(2):107-12. doi: 10.1161/01.cir.100.2.107.
The role of endogenous nitric oxide (NO) and cyclooxygenase metabolites was investigated in contractile responses of small omental arteries from patients with hyperdynamic septic shock.
Expression of inducible NO synthase (immunostaining) and a high but variable level of NO production (NO spin trapping) was detected in arteries from patients with septic shock. In these vessels, ex vivo contractile responses to the thromboxane A2 analogue U46619 and to low concentrations of norepinephrine (NE) (up to 10 micromol/L) were not significantly different from controls. However, higher concentrations of NE caused pronounced fading of contraction in septic but not in nonseptic arteries. Exposure to either the NO synthase inhibitor NG-nitro-L-arginine methyl ester or the cyclooxygenase inhibitor indomethacin had no effect in control vessels. However, both inhibitors increased the response to the contractile effects of the 2 agonists only in patients with septic shock. In contrast to NG-nitro-L-arginine methyl ester, which decreased the threshold concentration of the fading effect of NE, indomethacin abolished this effect in arteries from septic patients.
These results provide direct evidence for the induction of NO synthase in small arteries from patients with septic shock. They suggest that in these arteries, increased production of NO, in conjunction with vasodilatory cyclooxygenase metabolites, contributes to counteract hyperreactivity to agonists and decreases the cyclooxygenase product-mediated pronounced fading of contraction caused by a high concentration of NE.
研究内源性一氧化氮（NO）和环氧化酶代谢产物在高动力性感染性休克患者小网膜动脉收缩反应中的作用。
在感染性休克患者的动脉中检测到诱导型一氧化氮合酶的表达（免疫染色）以及高水平但变化不定的NO生成（NO自旋捕获）。在这些血管中，对血栓素A2类似物U46,619和低浓度去甲肾上腺素（NE）（高达10 μmol/L）的离体收缩反应与对照组无显著差异。然而，较高浓度的NE导致感染性休克患者的动脉出现明显的收缩消退，而非感染性休克患者的动脉则无此现象。给予一氧化氮合酶抑制剂NG-硝基-L-精氨酸甲酯或环氧化酶抑制剂吲哚美辛对对照血管无影响。然而，仅在感染性休克患者中，这两种抑制剂均增强了对两种激动剂收缩作用的反应。与降低NE消退效应阈值浓度的NG-硝基-L-精氨酸甲酯不同，吲哚美辛消除了感染性休克患者动脉中的这种效应。
这些结果为感染性休克患者小动脉中一氧化氮合酶的诱导提供了直接证据。结果提示，在这些动脉中，NO生成增加，连同血管舒张性环氧化酶代谢产物，有助于抵消对激动剂的高反应性，并减少高浓度NE引起的环氧化酶产物介导的明显收缩消退。
