Nava E, Palmer R M, Moncada S
Wellcome Research Laboratories, Beckenham, Kent, England.
J Cardiovasc Pharmacol. 1992;20 Suppl 12:S132-4. doi: 10.1097/00005344-199204002-00037.
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 micrograms/kg/h), the blood pressure was maintained at control levels and no mortality was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
在静脉注射伤寒沙门氏菌内毒素（脂多糖，4毫克/千克）后，于5小时内测定了一氧化氮（NO）在麻醉大鼠血压变化、血浆硝酸盐和亚硝酸盐（NOx）水平以及丙氨酸转氨酶（ALT）变化中的作用。用脂多糖处理的大鼠血压持续下降，同时血浆NOx和ALT升高。这些大鼠中有40%在实验过程中死亡。在脂多糖注射前1小时和注射后2小时用1毫克/千克地塞米松处理的大鼠血压无变化，且NOx和ALT的升高受到显著抑制。该组大鼠无一死亡。给予10毫克/千克的NG-单甲基-L-精氨酸（L-NMMA）可防止血压下降，并部分防止NOx和ALT升高。该组动物无一死亡。相比之下，300毫克/千克的L-NMMA导致血压先升高后迅速下降，并增强了ALT的升高，同时消除了NOx的升高。所有这些动物在实验结束前死亡。然而，当用高剂量L-NMMA处理的大鼠持续输注S-亚硝基-N-乙酰青霉胺（SNAP，300微克/千克/小时）时，血压维持在对照水平，且未观察到死亡情况。（摘要截取自250字）
