THE INDUCTION OF NITRIC-OXIDE SYNTHASE AND INTESTINAL VASCULAR-PERMEABILITY BY ENDOTOXIN IN THE RAT
THE INDUCTION OF NITRIC-OXIDE SYNTHASE AND INTESTINAL VASCULAR-PERMEABILITY BY ENDOTOXIN IN THE RAT
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DOI：
10.1111/j.1476-5381.1993.tb13940.x
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发表时间：
1993-11-01
影响因子：
7.3
通讯作者：
MONCADA, S
中科院分区：
文献类型：
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作者：
BOUGHTONSMITH, NK;EVANS, SM;MONCADA, S
1内毒素（E.研究了大鼠5小时内一氧化氮合酶（NOS）的诱导以及结肠和空肠血管通透性的变化。2在静息条件下，钙依赖性组成型NOS，通过放射性标记的L-精氨酸转化为瓜氨酸来确定，在结肠和空肠组织匀浆中均检测到。3给予内毒素（3 mg kg-1，i. v.）导致在2小时的滞后期后，在离体结肠和空肠中出现钙非依赖性NOS活性，这是诱导型NOS酶的特征。4施用内毒素导致在3小时的滞后期后结肠和空肠血管通透性增加，这通过放射性标记的白蛋白的渗漏来确定。5用地塞米松（1 mg kg-1 s.c.，6.给予NO合酶抑制剂N（G）-单甲基-L-精氨酸（12.5-50 mg kg-1，s.c.）内毒素注射后3 h，剂量依赖性地降低了随后空肠和结肠中血管通透性的增加，L-精氨酸（300 mg kg-1，s.c.）逆转了该作用。7这些结果表明，NOS的诱导与内毒素诱导的大鼠结肠和空肠血管损伤有关。
1 The effect of endotoxin (E. coli lipopolysaccharide) on the induction of nitric oxide synthase (NOS) and the changes in vascular permeability in the colon and jejunum over a 5 h period have been investigated in the rat.2 Under resting conditions, a calcium-dependent constitutive NOS, determined by the conversion of radiolabelled L-arginine to citrulline, was detected in homogenates of both colonic and jejunal tissue.3 Administration of endotoxin (3 mg kg-1, i.v.) led, after a 2 h lag period, to the appearance of calcium-independent NOS activity in the colon and jejunum ex vivo, characteristic of the inducible NOS enzyme.4 Administration of endotoxin led to an increase in colonic and jejunal vascular permeability after a lag period of 3 h, determined by the leakage of radiolabelled albumin.5 Pretreatment with dexamethasone (1 mg kg-1 s.c., 2 h prior to challenge) inhibited both the induction of NOS and the vascular leakage induced by endotoxin.6 Administration of the NO synthase inhibitor N(G)-monomethyl-L-arginine (12.5-50 mg kg-1, s.c.) 3 h after endotoxin injection, dose-dependently reduced the subsequent increase in vascular permeability in jejunum and colon, an effect reversed by L-arginine (300 mg kg-1, s.c.).7 These findings suggest that induction of NOS is associated with the vascular injury induced by endotoxin in the rat colon and jejunum.