Hock C E, Yin K, Yue G, Wong P Y
Department of Medicine, School of Osteopathic Medicine, University of Medicine and Dentistry of New Jersey, Stratford 08084, USA.
Am J Physiol. 1997 Feb;272(2 Pt 2):H843-50. doi: 10.1152/ajpheart.1997.272.2.H843.
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.
一氧化氮（NO）被认为与内毒素休克循环功能障碍的发病机制有关。我们研究了氨基胍（AG），一种对诱导型一氧化氮合酶（NOS）更具选择性的一氧化氮合酶抑制剂，对静脉注射大剂量（10mg/kg）脂多糖（LPS，肠炎沙门氏菌）后循环和炎症后遗症的影响。接受LPS+赋形剂（LPS+Veh）的大鼠在注射LPS后10分钟内平均动脉血压（MABP）下降73%，心脏指数（CI）和每搏量指数（SVI）下降50%。LPS注射后60、120和180分钟时，MABP分别恢复到64±3、81±6和79±8mmHg。然而，在整个实验期间，CI和SVI仍降低40-50%。LPS注射后180分钟时，全身血管阻力（SVRI）、心率（HR）和血细胞比容显著升高。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、心脏、肝脏和肠道组织中的亚硝酸盐/硝酸盐显著升高。AG治疗显著降低了血浆亚硝酸盐/硝酸盐，但未改变初始低血压或心脏抑制。然而，在LPS注射后60分钟时，与赋形剂相比，AG治疗的大鼠HR、MABP和SVRI更高，而CI和SVI仍降低。LPS后肺中髓过氧化物酶活性显著增加，但其他组织中未增加。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，静脉注射LPS后心血管功能抑制既不是由NO单独引起，也不是由急性炎症细胞积聚单独引起。
