The effects of nitric oxide in acute lung injury

被引:94
作者
Mehta, S [1 ]
机构
[1] Univ Western Ontario, Ctr Critical Illness Res, Lawson Hlth Res Inst, Div Resp,London Hlth Sci Ctr, London, ON N6A 4GS, Canada
[2] Univ Western Ontario, Dept Med, London, ON N6A 4GS, Canada
关键词
lung injury; nitric oxide; endothelial cell; neutrophil; macrophage; permeability;
D O I
10.1016/j.vph.2005.08.013
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Acute lung injury (ALI) is a common clinical problem associated with significant morbidity and mortality. Ongoing clinical and basic research and a greater understanding of the pathophysiology of ALI have not been translated into new anti-inflammatory therapeutic options for patients with ALI, or into a significant improvement in the outcome of ALI. In both animal models and humans with ALI, there is increased endogenous production of nitric oxide (NO) due to enhanced expression and activity of inducible NO synthase (iNOS). This increased presence of iNOS and NO in ALI contributes importantly to the pathophysiology of ALI. However, inhibition of total NO production or selective inhibition of iNOS has not been effective in the treatment of ALI. We have recently suggested that there may be differential effects of NO derived from different cell populations in ALI. This concept of cell-source-specific effects of NO in ALI has potential therapeutic relevance, as targeted iNOS inhibition specifically to key individual cells may be an effective therapeutic approach in patients with ALI. In this paper, we will explore the potential role for endogenous iNOS-derived NO in ALI. We will review the evidence for increased iNOS expression and NO production, the effects of nonselective NOS inhibition, the effects of selective inhibition or deficiency of iNOS, and this concept of cell-source-specific effects of iNOS in both animal models and human ALI. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:390 / 403
页数:14
相关论文
共 163 条
[1]   Inhibition of exhaled nitric oxide production during sepsis does not prevent lung inflammation [J].
Aaron, SD ;
Valenza, F ;
Volgyesi, G ;
Mullen, JBM ;
Slutsky, AS ;
Stewart, TE .
CRITICAL CARE MEDICINE, 1998, 26 (02) :309-314
[2]   Why immunomodulatory therapies have not worked in sepsis [J].
Abraham, E .
INTENSIVE CARE MEDICINE, 1999, 25 (06) :556-566
[3]   Nitric oxide modulates the catalytic activity of myeloperoxidase [J].
Abu-Soud, HM ;
Hazen, SL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (08) :5425-5430
[4]   LEUKOCYTE-ENDOTHELIAL INTERACTIONS AND REGULATION OF LEUKOCYTE MIGRATION [J].
ADAMS, DH ;
SHAW, S .
LANCET, 1994, 343 (8901) :831-836
[5]   Leukotoxin (9,10-epoxy-12-octadecenoate) impairs energy and redox state of isolated perfused rat lung [J].
Akai, M ;
Ishizaki, T ;
Matsukawa, S ;
Shigemori, K ;
Miyamori, I .
FREE RADICAL BIOLOGY AND MEDICINE, 1998, 25 (4-5) :596-604
[6]  
Allport JR, 2002, J LEUKOCYTE BIOL, V71, P821
[7]  
Amin AR, 1996, J INFLAMM, V47, P190
[8]   Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care [J].
Angus, DC ;
Linde-Zwirble, WT ;
Lidicker, J ;
Clermont, G ;
Carcillo, J ;
Pinsky, MR .
CRITICAL CARE MEDICINE, 2001, 29 (07) :1303-1310
[9]   Compartmentalised inducible nitric-oxide synthase activity in septic shock [J].
Annane, D ;
Sanquer, S ;
Sébille, V ;
Faye, A ;
Djuranovic, D ;
Raphaël, JC ;
Gajdos, P ;
Bellissant, E .
LANCET, 2000, 355 (9210) :1143-1148
[10]   Prolonged inhibition of nitric oxide synthesis in severe septic shock: A clinical study [J].
Avontuur, JAM ;
Nolthenius, RPT ;
van Bodegom, JW ;
Bruining, HA .
CRITICAL CARE MEDICINE, 1998, 26 (04) :660-667