The Role of Nitric Oxide in Endotoxic Shock: Effects of NG‐Monomethyl‐L‐Arginine
The Role of Nitric Oxide in Endotoxic Shock: Effects of NG‐Monomethyl‐L‐Arginine
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一氧化氮在内毒素休克中的作用：NG-单甲基-L-精氨酸的作用
DOI：
10.1097/00005344-199204002-00037
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发表时间：
1992
影响因子：
3
通讯作者：
S. Moncada
中科院分区：
文献类型：
--
作者：
E. Nava;R. Palmer;S. Moncada
摘要：在麻醉大鼠静脉注射伤寒沙门氏菌内毒素(LPS，4 mg/kg)5h后，观察了一氧化氮(NO)在血压及血浆硝酸盐、亚硝酸盐(NOx)和丙氨酸氨基转移酶(ALT)水平变化中的作用。接受内毒素治疗的大鼠血压持续下降，同时血浆NOx和ALT升高。其中40%的老鼠在实验中死亡。地塞米松(1 mg/kg)给药后1h和2 h，大鼠血压无明显变化，对NOx和ALT的升高有明显抑制作用。这组大鼠中没有一只死亡。给予10 mg/kg的单甲基L精氨酸(L-NMMA)可阻止血压的下降，并部分阻止NOx和ALT的升高。这组动物中没有一只死亡。而L-NMMA300 mg/kg可引起血压先升高后迅速下降，并使ALT升高，同时消除NOx升高。所有这些动物都在实验结束前死亡。而给予大剂量L-N-乙酰青霉胺(300μg/kg/h)后，血压维持在对照水平，无死亡病例。这些结果表明，诱导型NO合酶合成的NO在内毒素休克的降压和组织损伤中起一定作用，决定L-NMMA利弊的关键因素是抑制NO合成的程度。
Summary: The role of nitric oxide (NO) in the changes in blood pressure and plasma levels of nitrate and nitrite (NOx) and alanine aminotransferase (ALT) were determined over a 5‐h period in anesthesized rats after intravenous administration of S. typhosa endotoxin (LPS, 4 mg/kg). Rats treated with LPS showed a sustained fall in blood pressure accompanied by an increase in plasma NOx and ALT. Forty percent of these rats died during the experiment. There was no change in blood pressure in rats treated with dexamethasone (1 mg/kg) 1 h before and 2 h after LPS and the increase in NOx and ALT was significantly inhibited. None of the rats in this group died. Administration of 10 mg/kg of NG‐monomethyl‐L‐arginine (l‐NMMA) prevented the fall in blood pressure and partially prevented the increase in NOx and ALT. None of the animals in this group died. In contrast, 300 mg/kg of l‐NMMA caused an initial increase in blood pressure followed by a rapid fall and enhanced the increase in ALT while abolishing the elevation of NOx. All of these animals died before the end of the experiment. However, when rats treated with high doses of l‐NMMA were given a continuous infusion of S‐nitroso‐N‐acetylpenicillamine (SNAP, 300 μg/kg/h), the blood pressure was maintained at control levels and no mortality was observed. These results indicate that the NO synthetized by the inducible NO synthase plays a role in the hypotension and tissue damage of endotoxic shock and that the critical factor determining the difference between a beneficial or an adverse effect of l‐NMMA is the degree of inhibition of NO synthesis.