Ketteler M, Cetto C, Kirdorf M, Jeschke G S, Schäfer J H, Distler A
Department of Endocrinology and Nephrology, University Hospital Benjamin Franklin, Free University of Berlin, Germany.
Kidney Int Suppl. 1998 Feb;64:S27-30.
Nitric oxide (NO) is an effector molecule with multiple effects on various organ systems. The most prominent physiological actions of NO as a biological mediator include cGMP-dependent vasodilation and cytotoxicity against pathogens in the unspecific immune defense. Sepsis syndrome is a complex disease entity mostly caused by overwhelming bacterial infections. It has a high mortality rate of 40 to 60%. Catecholamine-resistant hypotension and myocardial depression are regarded as major factors contributing to death in septic patients. In septic shock, a pathophysiologically increased NO production occurs due to an excessive induction of the inducible NO synthase (iNOS). Inducible nitric oxide synthase up-regulation is probably caused by bacterial endo- and exotoxins as well as by an increase of circulating pro-inflammatory cytokines. It may be a key factor leading to pronounced vasodilation and myocardial toxicity. Experimental studies have confirmed that NO overproduction causes severe hypotension in septic animals. Treatment with competitive NOS-inhibitors abolishes this hypotension in animals as well as in septic patients. However, their use is complicated by concomitant decreases in cardiac index and oxygen delivery. Conclusive data on mortality in animals and patients with sepsis-syndrome treated by NOS antagonists are not available. This article discusses current concepts concerning the L-arginine/NO system in the pathophysiology of and as a potential therapeutic target in septic shock.
一氧化氮（NO）是一种对多种器官系统有多种作用的效应分子。NO作为生物介质最显著的生理作用包括依赖环磷酸鸟苷（cGMP）的血管舒张以及在非特异性免疫防御中对病原体的细胞毒性。脓毒症综合征是一种主要由严重细菌感染引起的复杂疾病实体。它的死亡率很高，在40%至60%之间。对儿茶酚胺抵抗的低血压和心肌抑制被认为是脓毒症患者死亡的主要因素。在脓毒症休克中，由于诱导型一氧化氮合酶（iNOS）的过度诱导，会出现病理生理上一氧化氮生成增加的情况。诱导型一氧化氮合酶上调可能是由细菌内毒素和外毒素以及循环促炎细胞因子的增加引起的。它可能是导致明显血管舒张和心肌毒性的关键因素。实验研究证实，一氧化氮过量生成会导致脓毒症动物出现严重低血压。用竞争性一氧化氮合酶抑制剂治疗可消除动物以及脓毒症患者的这种低血压。然而，使用它们会因心脏指数和氧输送同时降低而变得复杂。关于一氧化氮合酶拮抗剂治疗脓毒症综合征动物和患者死亡率的确切数据尚无定论。本文讨论了有关L-精氨酸/一氧化氮系统在脓毒症休克病理生理学中以及作为潜在治疗靶点的当前概念。
