Effects of inhibition of nitric oxide synthase by aminoguanidine in acute endotoxemia.
Effects of inhibition of nitric oxide synthase by aminoguanidine in acute endotoxemia.
复制标题
氨基胍对急性内毒素血症一氧化氮合酶的抑制作用。
DOI：
10.1152/ajpheart.1997.272.2.h843
复制
发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Wong,PY
中科院分区：
文献类型：
--
作者：
Hock,CE;Yin,K;Yue,G;Wong,PY
一氧化氮（NO）参与了内毒素休克循环功能障碍的发病机制。我们研究了氨基胍（AG），一种一氧化氮合酶（NOS）抑制剂，对诱导的NOS更具选择性，在给药后（10 mg/kg iv）脂多糖（LPS）（肠炎沙门氏菌）循环和炎症后遗症的影响。LPS +载药（LPS + Veh）给药后10 min内，大鼠平均动脉血压（MABP）下降73%，心脏指数（CI）和SV指数（SVI）下降50%。lps后60、120和180分钟，MABP分别恢复到64 +/- 3、81 +/- 6和79 +/- 8 mmHg。然而，CI和SVI在整个实验期间仍保持40-50%的下降。给药后180分钟，全身血管阻力（SVRI）、心率（HR）和红细胞压积显著升高。急性内毒素血症3小时后，血浆亚硝酸盐/硝酸盐增加15倍，肺、心、肝和肠组织亚硝酸盐/硝酸盐显著升高。AG治疗可显著降低血浆亚硝酸盐/硝酸盐，但未改变初始低血压或心脏抑制。然而，在LPS给药后60分钟，ag处理大鼠的HR、MABP和SVRI比对照大鼠高，而CI和SVI仍然下降。LPS处理后，肺髓过氧化物酶活性显著升高，而其他组织无明显升高。与LPS + Veh相比，AG输注显著降低了肺和心脏组织中的亚硝酸盐/硝酸盐。数据表明，一氧化氮和急性炎症细胞积聚都不是静脉注射LPS后心血管功能下降的唯一原因。
Nitric oxide (NO) has been implicated in the pathogenesis of the circulatory dysfunction of endotoxin shock. We investigated the effect of aminoguanidine (AG), an inhibitor of nitric oxide synthase (NOS) that is more selective for the inducible NOS, on the circulatory and inflammatory sequelae after administration of a bolus (10 mg/kg iv) of lipopolysaccharide (LPS) (Salmonella enteritidis). Rats receiving LPS + vehicle (LPS + Veh) exhibited a 73% decrease in mean arterial blood pressure (MABP) and a 50% decrease in cardiac index (CI) and SV index (SVI) within 10 min after LPS administration. MABP recovered to 64 +/- 3, 81 +/- 6, and 79 +/- 8 mmHg, at 60, 120, and 180 min post-LPS, respectively. However, CI and SVI remained depressed by 40-50% for the entire experimental period. Systemic vascular resistance (SVRI), heart rate (HR), and hematocrit were significantly elevated at 180 min after LPS administration. There was a 15-fold increase in plasma nitrite/nitrate and significantly elevated tissue nitrite/nitrate in the lung, heart, liver, and intestine after 3 h of acute endotoxemia. Treatment with AG markedly decreased plasma nitrite/nitrate but did not alter the initial hypotension or cardiac depression. However, at 60 min after LPS administration the HR, MABP, and SVRI were higher in the AG-treated rats compared with vehicle, whereas CI and SVI remained depressed. Myeloperoxidase activity was significantly increased in the lung but not in the other tissues after LPS. The AG infusion significantly reduced tissue nitrite/nitrate in the lung and heart compared with LPS + Veh. The data suggest that neither NO nor acute inflammatory cell accumulation is solely responsible for the depressed cardiovascular function after intravenous administration of LPS.