Vallance P, Moncada S
Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, London, UK.
New Horiz. 1993 Feb;1(1):77-86.
Nitric oxide synthesized by a constitutive enzyme is a widespread mediator of cell-cell and intracellular communication. This mediator provides a continuous vasodilator influence in the cardiovascular system, modifies the function of circulating cells, and acts as a neurotransmitter. After exposure to bacterial endotoxin or certain cytokines, expression of a second, inducible nitric oxide synthase occurs in a wide variety of tissues. This enzyme produces large amounts of nitric oxide for long periods and has been implicated in pathophysiologic changes seen in sepsis. In some cells, including macrophages, the nitric oxide synthesized by the inducible enzyme is toxic and appears to be an important mediator in host defense. Studies in animals and in vitro have demonstrated that nitric oxide released from inducible nitric oxide synthase in other tissues may cause profound vasodilation, damage to host cells, and cardiac dysfunction. The hypotension of endotoxin- or cytokine-induced shock can be reversed by inhibitors of nitric oxide synthase and these agents may provide a novel therapeutic approach to the treatment of severe septic shock. Preliminary studies in humans suggest that inhibition of nitric oxide synthase improves BP and stabilizes hemodynamics; effects on mortality rates remain to be determined.
由一种组成型酶合成的一氧化氮是细胞间和细胞内通讯中广泛存在的介质。这种介质在心血管系统中持续发挥血管舒张作用，改变循环细胞的功能，并作为神经递质起作用。在接触细菌内毒素或某些细胞因子后，第二种诱导型一氧化氮合酶在多种组织中表达。这种酶长期产生大量一氧化氮，并与脓毒症中出现的病理生理变化有关。在包括巨噬细胞在内的一些细胞中，由诱导型酶合成的一氧化氮具有毒性，似乎是宿主防御中的一种重要介质。动物和体外研究表明，其他组织中诱导型一氧化氮合酶释放的一氧化氮可能导致严重的血管舒张、宿主细胞损伤和心脏功能障碍。一氧化氮合酶抑制剂可逆转内毒素或细胞因子诱导的休克低血压，这些药物可能为严重脓毒症休克的治疗提供一种新的治疗方法。对人类的初步研究表明，抑制一氧化氮合酶可改善血压并稳定血流动力学；对死亡率的影响仍有待确定。
