Wolfe T A, Dasta J F
College of Pharmacy, Ohio State University, Columbus 43210.
Ann Pharmacother. 1995 Jan;29(1):36-46. doi: 10.1177/106002809502900108.
To review the current literature regarding the role of nitric oxide (NO) in the pathogenesis of septic shock and to describe the potential role of NO synthase (NOS) inhibitors in the treatment of septic shock.
A MEDLINE, Cancerlit, Biosis, Scisearch, CBAC, bibliography, and current journal search of applicable articles on the involvement of NO in mediating septic shock and the use of NOS inhibitors in septic shock was conducted. Articles that were searched included animal and human studies from January 1990 to August 1994.
Because of the preliminary nature of the research involving NOS inhibitors in septic shock, all available studies were evaluated.
NO appears to have a role in the mediation of the hemodynamic instability associated with septic shock. Cytokines and endotoxin stimulate synthesis of the inducible NOS, which produces large amounts of NO over an extended period of time. NO may be the key mediator in the pathogenesis of septic shock. Derivatives of the precursor to NO, L-arginine, have been used to investigate the role of NO in septic shock and as possible therapeutic agents. Comparison of study results among animal studies shows much variability. This variability may be attributable to differences in dosing regimens and models of septic shock. Data obtained from human studies are more consistent, but are limited to a few case series. Results indicate that NOS inhibitors increase blood pressure and systemic vascular resistance and decrease cardiac output. The effects of NOS inhibitors on morbidity and mortality have not been assessed because of the lack of an appropriate sample size.
NO appears to play a role in septic shock; however, the use of NOS inhibitors to treat septic shock requires further studies to determine an appropriate dosing regimen and to determine the effects of these agents on morbidity and mortality.
回顾关于一氧化氮（NO）在感染性休克发病机制中作用的当前文献，并描述一氧化氮合酶（NOS）抑制剂在感染性休克治疗中的潜在作用。
对MEDLINE、Cancerlit、Biosis、Scisearch、CBAC、参考文献以及当前期刊进行检索，以查找关于NO参与介导感染性休克以及NOS抑制剂在感染性休克中应用的相关适用文章。检索的文章包括1990年1月至1994年8月的动物和人体研究。
由于涉及NOS抑制剂治疗感染性休克的研究尚处于初步阶段，因此对所有可得研究进行了评估。
NO似乎在介导与感染性休克相关的血流动力学不稳定中起作用。细胞因子和内毒素刺激诱导型NOS的合成，该酶可在较长时间内产生大量NO。NO可能是感染性休克发病机制中的关键介质。NO的前体L-精氨酸的衍生物已被用于研究NO在感染性休克中的作用，并作为可能的治疗药物。动物研究之间的结果比较显示出很大的变异性。这种变异性可能归因于给药方案和感染性休克模型的差异。从人体研究获得的数据更一致，但仅限于少数病例系列。结果表明，NOS抑制剂可升高血压和全身血管阻力，并降低心输出量。由于样本量不足，尚未评估NOS抑制剂对发病率和死亡率的影响。
NO似乎在感染性休克中起作用；然而，使用NOS抑制剂治疗感染性休克需要进一步研究，以确定合适的给药方案，并确定这些药物对发病率和死亡率的影响。
