Dutta P, Ryan D E, Tabrizchi R
Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
Jpn J Pharmacol. 2001 Mar;85(3):241-9. doi: 10.1254/jjp.85.241.
Administration of bacterial endotoxin (lipopolysaccharide, LPS) intravenously has been noted to produce a shock state, which is characterized by hypotension and multi-organ system failure. The aim of the present investigation was to (a) examine the influence of rolipram on hemodynamics, plasma levels of tumor necrosis factor-alpha (TNF-alpha) levels, and production of inducible nitric oxide synthase (iNOS) in the lungs, ex vivo, in LPS-treated rats, and (b) determine the cardiovascular effects of a selective alpha1-adrenoceptor agonist, methoxamine, in the absence or presence of rolipram in rats treated with LPS. Blood pressure, cardiac index, heart rate and arterial resistance were assessed in Long-Evans rats anesthetized with thiobutabarbital. Administration of LPS to animals resulted in a significant reduction in cardiac index over time. The administration of LPS to rats resulted in a substantial rise in the plasma levels of TNF-alpha. Furthermore, the injection of LPS resulted in a significant increase in the iNOS activity in the lungs. Pre-treatment with rolipram prevented the decline in cardiac index in animals that received LPS. Infusion of methoxamine into animals injected with rolipram and pre-treated with LPS did not result in significant changes in cardiac index. Pre-treatment with rolipram or dexamethasone in animals injected with LPS significantly prevented the rise in TNF-alpha when compared to the respective values in vehicle-treated animals. Our present observations support the view that the cardiac index can be maintained in animals treated with LPS independent of iNOS inhibition.
静脉注射细菌内毒素（脂多糖，LPS）已被注意到会产生一种休克状态，其特征为低血压和多器官系统衰竭。本研究的目的是：（a）在体外研究咯利普兰对LPS处理的大鼠的血流动力学、肿瘤坏死因子-α（TNF-α）血浆水平以及肺中诱导型一氧化氮合酶（iNOS）产生的影响；（b）确定在LPS处理的大鼠中，在不存在或存在咯利普兰的情况下，选择性α1-肾上腺素能受体激动剂甲氧明的心血管效应。在用硫喷妥巴比妥麻醉的Long-Evans大鼠中评估血压、心脏指数、心率和动脉阻力。给动物注射LPS会导致心脏指数随时间显著降低。给大鼠注射LPS会导致TNF-α血浆水平大幅升高。此外，注射LPS会导致肺中iNOS活性显著增加。用咯利普兰预处理可防止接受LPS的动物心脏指数下降。向注射咯利普兰并经LPS预处理的动物输注甲氧明不会导致心脏指数发生显著变化。与载体处理动物的相应值相比，在用LPS注射的动物中用咯利普兰或地塞米松预处理可显著防止TNF-α升高。我们目前的观察结果支持这样一种观点，即在用LPS处理的动物中可以维持心脏指数，而与iNOS抑制无关。
