REVERSAL OF ENDOTOXIN-MEDIATED SHOCK BY NG-METHYL-L-ARGININE, AN INHIBITOR OF NITRIC-OXIDE SYNTHESIS
REVERSAL OF ENDOTOXIN-MEDIATED SHOCK BY NG-METHYL-L-ARGININE, AN INHIBITOR OF NITRIC-OXIDE SYNTHESIS
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DOI：
10.1016/0006-291x(90)91565-a
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发表时间：
1990-11-15
影响因子：
3.1
通讯作者：
LODATO, RF
中科院分区：
文献类型：
--
作者：
KILBOURN, RG;JUBRAN, A;LODATO, RF
感染性休克是一种因接触细菌内毒素而导致的危及生命的疾病。它表现为心血管衰竭，并由肿瘤坏死因子等细胞因子的释放介导。其中一些细胞因子导致血管活性物质的释放。在本研究中，给狗施用40μg/kg的细菌内毒素，在30至90分钟内导致外周血管阻力下降33％，平均动脉血压下降54％。静脉注射 NG-甲基-L-精氨酸（20 mg/kg）（一种有效的选择性一氧化氮合成抑制剂）后，血管阻力和全身动脉压在 1.5 分钟内恢复正常。 L-精氨酸逆转L-NMA 的作用并恢复内毒素引起的低血压。尽管注射 NG-甲基-L-精氨酸会增加对照犬的血压，但在内毒素血症犬中的高血压效应要大得多（24.8 .+-. 2.7 mmHg vs. 47.8 .+-. 6.8 mmHg，p = 0.01，n = 4）。 NG-甲基-L-精氨酸仅引起因连续静脉输注硝酸甘油而导致低血压的狗的血压适度升高（17.1.+-.5.0 mm Hg，n = 3）。这些发现表明一氧化氮过量产生是内毒素休克的一个重要因素。此外，我们的研究结果首次证明一氧化氮合成抑制剂在内毒素性休克中的效用，并表明此类抑制剂在感染性休克的治疗中可能具有治疗价值。
Septic shock is a life-threatening condition that results from exposure to bacterial endotoxin. It is manifested by cardiovascular collapse and mediated by the release of cytokines such as tumor necrosis factor. Some of these cytokines cause the release of vasoactive substances. In the present study, administration of 40 .mu.g/kg of bacterial endotoxin to dogs caused a 33% decrease in peripheral vascular resistance and a 54% fall in mean arterial blood pressure within 30 to 90 minutes. Vascular resistance and systemic arterial pressure returned to normal within 1.5 minutes after intravenous administration of NG-methyl-L-arginine (20 mg/kg), a potent and selective inhibitor of nitric oxide synthesis. L-Arginine reversed the effect of L-NMA and restored the endotoxin-induced hypotension. Although NG-methyl-L-arginine injection increased blood pressure in control dogs, the hypertensive effect was much greater in endotoxemic dogs (24.8 .+-. 2.7 mmHg vs. 47.8 .+-. 6.8 mmHg, p = 0.01, n = 4). NG-Methyl-L-arginine caused only a modest increase in blood pressure in dogs made hypotensive by continuous intravenous infusion of nitroglycerin (17.1 .+-. 5.0 mm Hg, n = 3). These findings suggest that nitric oxide overproduction is an important contributor to endotoxic shock. Moreover, our findings demonstrate for the first time, the utility of nitric oxide synthesis inhibitors in endotoxic shock and suggest that such inhibitors may be of therapeutic value in the treatment of septic shock.