Mitaka C, Hirata Y, Ichikawa K, Uchida T, Yokoyama K, Nagura T, Tsunoda Y, Amaha K
Department of Intensive Care, Tokyo Medical and Dental University, Japan.
Am J Physiol. 1995 May;268(5 Pt 2):H2017-23. doi: 10.1152/ajpheart.1995.268.5.H2017.
To elucidate the role of nitric oxide (NO) in septic shock, we measured hemodynamic and pulmonary gas changes in anesthetized dogs after intravenous administration of bacterial lipopolysaccharide (LPS) with or without NO synthase inhibitor, NG-nitro-L-arginine (L-NNA). Infusion of LPS (250 ng.kg-1.min-1) for 2 h decreased mean arterial pressure over 1-4 h. Although L-NNA (10 mg/kg) blocked LPS-induced hypotension, it decreased cardiac index, oxygen delivery index, arterial pH, and arterial PO2 and increased systemic vascular resistance index in the presence or absence of LPS. Administration of NG-nitro-D-arginine (D-NNA, 10 mg/kg) alone caused fewer hemodynamic effects (increased systemic vascular resistance index and decreased cardiac index) than L-NNA alone. Our study provides evidence that L-NNA prevents endotoxin-induced hypotension but decreases cardiac output and oxygen delivery, effects that may, in part, be due to a nonspecific NO synthase-independent event. Thus clinical use of NO synthase inhibitors for the treatment of septic shock should be cautiously considered.
为阐明一氧化氮（NO）在脓毒性休克中的作用，我们在麻醉犬静脉注射细菌脂多糖（LPS）（伴或不伴NO合酶抑制剂NG-硝基-L-精氨酸（L-NNA））后，测量其血流动力学和肺气体变化。以250 ng·kg⁻¹·min⁻¹的剂量输注LPS 2小时，可使平均动脉压在1 - 4小时内降低。尽管L-NNA（10 mg/kg）可阻断LPS诱导的低血压，但在有或无LPS存在的情况下，它都会降低心脏指数、氧输送指数、动脉pH值和动脉血氧分压，并增加全身血管阻力指数。单独给予NG-硝基-D-精氨酸（D-NNA，10 mg/kg）比单独给予L-NNA引起的血流动力学效应更少（全身血管阻力指数增加和心脏指数降低）。我们的研究提供了证据，表明L-NNA可预防内毒素诱导的低血压，但会降低心输出量和氧输送，这些效应可能部分归因于非特异性的不依赖NO合酶的事件。因此，对于NO合酶抑制剂在脓毒性休克治疗中的临床应用应谨慎考虑。
