Smith R E, Palmer R M, Moncada S
Wellcome Research Laboratories, Beckenham, Kent.
Br J Pharmacol. 1991 Sep;104(1):5-6. doi: 10.1111/j.1476-5381.1991.tb12375.x.
The coronary vasoconstriction induced by the thromboxane mimetic U46619 (9, 11 dideoxy methanoepoxy 9 alpha, 11 alpha prostaglandin F2 alpha, 3-30 nM) was significantly attenuated in hearts obtained from rabbits treated with endotoxin (lipopolysaccharide, LPS, 200 micrograms kg-1, i.v.) 4 h before isolation of the heart. Under these conditions the vasoconstriction induced by two inhibitors of nitric oxide (NO) synthase, NG-monomethyl-L-arginine (L-NMMA) and N-iminoethyl-L-ornithine (L-NIO) (1-100 microM for each) was significantly enhanced when compared to that induced in hearts from control animals. Both the decreased response to U46619 and the increased response to inhibitors of NO synthase were significantly attenuated by administration of dexamethasone (4 mg kg-1, i.v.) 90 min before treatment with LPS. These data are consistent with the induction, by LPS, of an NO synthase, and the inhibition of this induction by dexamethasone. The enhanced NO synthesis contributes to the haemodynamic changes known to occur in endotoxin shock.
在心脏分离前4小时用内毒素（脂多糖，LPS，200微克/千克，静脉注射）处理的兔心脏中，血栓素类似物U46619（9,11-二脱氧甲氧基环氧9α，11α前列腺素F2α，3 - 30 nM）诱导的冠状动脉血管收缩明显减弱。在这些条件下，与对照动物心脏相比，两种一氧化氮（NO）合酶抑制剂NG-单甲基-L-精氨酸（L-NMMA）和N-亚氨基乙基-L-鸟氨酸（L-NIO）（每种1 - 100 microM）诱导的血管收缩明显增强。在用LPS处理前90分钟静脉注射地塞米松（4毫克/千克），对U46619的反应降低和对NO合酶抑制剂的反应增加均明显减弱。这些数据与LPS诱导NO合酶以及地塞米松抑制这种诱导作用一致。增强的NO合成导致了内毒素休克中已知发生的血流动力学变化。
