Protective and pathological roles of nitric oxide in endotoxin shock.
Protective and pathological roles of nitric oxide in endotoxin shock.
复制标题
一氧化氮在内毒素休克中的保护和病理作用。
DOI：
10.1093/cvr/26.1.48
复制
发表时间：
1992
影响因子：
10.8
通讯作者：
S. Moncada
中科院分区：
文献类型：
--
作者：
C. Wright;D. Rees;S. Moncada
客观化
目的：观察钙离子依赖性和诱导型一氧化氮合酶(NO)合成酶的抑制剂L精氨酸(NMMA)或糖皮质激素地塞米松对内毒素休克的影响。
方法
测定了49只氟烷麻醉的新西兰白兔静脉注射明尼苏达沙门氏菌500微克·kg~(-1)后，平均动脉压、门静脉、肝动脉和后肢血管床的血流量。观察L-NMMA(300 mg·kg~(-1)静脉注射)和地塞米松(3 mg·kg~(-1)静脉注射)对内毒素治疗前后的影响。本文还观察了静脉注射一氧化氮供体S-亚硝基-N-乙酰青霉胺(SNAP，300微克·kg~(-1)·h~(-1))对内毒素和L-NMMA作用的影响。
结果
脂多糖引起平均动脉压最初的短暂下降和血管床中血流量的减少，随后平均动脉压逐渐下降。在脂多糖之前或之后给予L-NMMA均明显加剧其作用，并导致严重的低血压、强烈的血管收缩和增加死亡率。地塞米松预处理对脂多糖后的初始血流动力学改变没有影响，但阻止了随后观察到的单用脂多糖治疗的动物平均动脉压的下降。然而，地塞米松未能保护同样在内毒素之前使用L-NMMA的动物。与对照组(单纯内毒素)或内毒素和L-NMMA组相比，经L-NMMA和SNAP预处理的动物血流动力学改变明显减轻。
结论
在内毒素血症中抑制结构性和诱导性一氧化氮合酶是有害的。这可以通过静脉内用NO供体取代NO来克服。然而，选择性地抑制诱导型一氧化氮合酶在休克中可能是有益的。
OBJECTIVE
The aim was to investigate the effects of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of both the constitutive (Ca2+ dependent) and inducible (Ca2+ independent) nitric oxide (NO) synthases, or of pretreatment with the glucocorticoid dexamethasone, an inhibitor of the induction of the Ca2+ independent NO synthase, on lipopolysaccharide induced shock in the anaesthetised rabbit.
METHODS
Mean arterial blood pressure, and blood flow in the portal vein, hepatic artery, and hindquarter vascular beds were measured in 49 halothane anaesthetised New Zealand White rabbits given lipopolysaccharide (Salmonella minnesota, 500 micrograms.kg-1 intravenously). The effects of pre- or post-lipopolysaccharide treatment with L-NMMA (300 mg.kg-1 intravenously) and of pretreatment with dexamethasone (3 mg.kg-1 intravenously) were determined. The effect of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP, 300 micrograms.kg-1.h-1 intravenously) in animals treated with lipopolysaccharide and L-NMMA was also studied.
RESULTS
Lipopolysaccharide elicited an initial transient fall in mean arterial pressure and decreases in blood flow in the vascular beds, followed by a progressive fall in mean arterial pressure. L-NMMA when given either before or after lipopolysaccharide markedly exacerbated its effects and resulted in severe hypotension, intense vasoconstriction, and increased mortality. Pretreatment with dexamethasone had no effect on the initial haemodynamic changes following lipopolysaccharide, but prevented the subsequent fall in mean arterial pressure observed in animals treated with lipopolysaccharide alone. Dexamethasone failed, however, to protect animals also treated with L-NMMA before lipopolysaccharide. Animals pretreated with L-NMMA and SNAP showed reduced haemodynamic changes when compared with controls (lipopolysaccharide only) or lipopolysaccharide and L-NMMA treated animals.
CONCLUSIONS
Inhibition of both constitutive and inducible NO synthases during endotoxaemia is deleterious. This can be overcome by replacing NO intravenously with a donor of NO. Selective inhibition of the inducible NO synthase may, however, be beneficial in shock.