Division of Pulmonary and Critical Care Medicine, University of California Davis, CA 95817, USA.
Expert Rev Respir Med. 2009 Oct;3(5):511-21. doi: 10.1586/ers.09.39.
Sepsis is a state of systemic inflammation directed at microbes or their toxins in blood or tissues. Nitric oxide (NO) is one of many vasoactive molecules released from a variety of cell types during sepsis. Almost two decades ago, NO emerged as a potential therapeutic target in sepsis. NO produced by the constitutive NO synthase (NOS) isoform (endothelial NOS and neuronal NOS) in the vascular endothelium and elsewhere acts as a nonadrenergic, noncholinergic neurotransmitter, an inhibitor of platelet aggregation and a vasodilator. During sepsis, activation of inducible NOS (iNOS) in the lung epithelium and other organs occurs, leading to NO overproduction. The result of excessive circulating NO is enhanced bacterial destruction, but also profound vasodilatation, activation of inflammatory cascades and depression of cardiac function. Trials of nonselective NOS inhibitors have shown increased mean arterial pressure, but also increased pulmonary artery pressure and reduced cardiac output. Small animal studies of iNOS selective inhibition have produced dichotomous results, but larger clinical studies assessing mortality are lacking. Inhaled NO has been touted as a therapeutic option to improve systemic oxygenation in the acute lung injury of sepsis (hypoxic pulmonary vasoconstriction and pulmonary hypertension); however, studies of inhaled NO in acute respiratory distress syndrome have not shown survival efficacy. Further investigation into the role of NO in human sepsis, and the development of methods to assess NO balance in patients with sepsis is essential in this field. In this review, we outline the effects of NO in sepsis, and summarize the therapeutic outcomes of NOS inhibitors, and inhaled NO in sepsis and acute respiratory distress syndrome.
脓毒症是一种全身性炎症状态，针对的是血液或组织中的微生物或其毒素。一氧化氮（NO）是脓毒症期间多种细胞类型释放的许多血管活性分子之一。大约二十年前，NO 作为脓毒症的潜在治疗靶点出现。血管内皮和其他部位的组成型一氧化氮合酶（NOS）同工型（内皮型 NOS 和神经元型 NOS）产生的 NO 作为非肾上腺素能、非胆碱能神经递质，血小板聚集抑制剂和血管扩张剂。在脓毒症期间，肺上皮和其他器官中的诱导型 NOS（iNOS）激活会导致 NO 过度产生。过量循环 NO 的结果是增强细菌破坏，但也会导致严重的血管扩张、炎症级联激活和心脏功能抑制。非选择性 NOS 抑制剂的试验显示平均动脉压升高，但肺动脉压升高和心输出量降低。iNOS 选择性抑制的小动物研究产生了二分结果，但缺乏评估死亡率的大型临床研究。吸入 NO 已被吹捧为改善脓毒症急性肺损伤（低氧性肺血管收缩和肺动脉高压）中全身氧合的治疗选择；然而，吸入 NO 在急性呼吸窘迫综合征中的研究并未显示出生存疗效。在该领域，进一步研究 NO 在人类脓毒症中的作用以及开发评估脓毒症患者 NO 平衡的方法至关重要。在这篇综述中，我们概述了 NO 在脓毒症中的作用，并总结了 NOS 抑制剂和吸入 NO 在脓毒症和急性呼吸窘迫综合征中的治疗结果。
