Role of Nitric Oxide in Vascular Permeability after Combined Burns and Smoke Inhalation Injury

Soejima, Kazutaka; Traber, Lillian D.; Schmalstieg, Frank C.; Hawkins, Hal K.; Jodoin, Jeffrey M.; Szabó, Csaba; Szabó, Éva; Varig, Lasio; Salzman, Andrew L.; Traber, Daniel L.

doi:10.1164/ajrccm.163.3.9912052

Cited by 123 publications

(109 citation statements)

References 26 publications

Supporting

Mentioning

100

Contrasting

Unclassified

Order By: Relevance

“…22 Whereas constitutively expressed endothelial NOSproduced NO is considered to have protective effects on the vessel wall, iNOS may have an important role in mediating oxidative stress. 23 In addition, iNOS is also involved in the process of healing after injury. 24 Mechanical injury to the vessel wall is associated with increased iNOS expression.…”

Section: Discussionmentioning

confidence: 99%

“…The rodent model has been reported to produce notoriously high levels of NO compared with larger animals. 23 It is currently unclear how uncoupling may occur in CS-exposed mice. However, it is notable that L-arginine treatment prevented endothelial dysfunction in rabbits exposed to tobacco smoke and normalized coronary vasomotion in long-term smokers.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of Exposure to Cigarette Smoke on Carotid Artery Intimal Thickening

Anazawa

Dimayuga

et al. 2004

ATVB

View full text Add to dashboard Cite

Objective-We investigated the role of inducible NO synthase (iNOS) in intimal thickening with exposure to cigarette smoke (CS). Methods and Results-Intimal thickening in wild-type (WT) and iNOS-deficient (iNOSϪ/Ϫ) mice subjected to CS exposure was induced by placement of a cuff around the carotid artery. CS exposure in WT mice was associated with increased arterial iNOS expression, superoxide production, activator protein-1 (AP-1) activation, and serum NO. 4,5 In the Atherosclerosis Risk in Communities Study, active smoking and exposure to environmental tobacco smoke were associated with accelerated progression of intimal/medial thickness of the carotid artery. 6 The underlying mechanism(s) of these deleterious effects remain unknown. 7,8 Increased transcription factor activation, expression of adhesion molecules, and redox gene inducible NO synthase (iNOS) have been demonstrated with exposure to cigarette smoke (CS) 9 -11 and may contribute to increased intimal thickening.The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor mediating enzyme induction in response to CS and may have a potentiating effect on CS carcinogenicity. 12 The mouse iNOS promoter 13 contains a site that corresponds to the core xenobiotic-responsive element (XRE) to which the AhR binds. Therefore, the AhR may mediate the negative effects of CS on the arterial intima.We hypothesized that exposure to CS increases iNOS gene expression and activity in the arterial wall leading to augmented intimal thickening after injury. We used a model of intimal thickening induced by placement of a periadventitial cuff around the right carotid artery of mice exposed to CS. Cultured aortic smooth muscle cells (SMCs) were used to investigate the AhR pathway for increased iNOS expression after exposure to CS condensate (CSC). Materials and Methods AnimalsMale wild-type (WT) and iNOS-deficient (iNOSϪ/Ϫ) mice with the C57BL/6J background strain (The Jackson Laboratory) were fed normal chow throughout the study period. At the age of 25 weeks, mice were anesthetized with Avertin (0.016 mL/g of 2.5% solution IP), and the right carotid artery was carefully isolated under a dissecting microscope. A nonocclusive plastic cuff was placed around the right carotid artery, and the skin incision was closed, as described previously. 14 Mice were euthanized 3, 7, or 21 days after cuff placement. The carotid arteries were perfused with 0.9% saline

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of Exposure to Cigarette Smoke on Carotid Artery Intimal Thickening

Anazawa

Dimayuga

et al. 2004

ATVB

View full text Add to dashboard Cite

show abstract

“…Kristof and colleagues showed that NOS2 knockout mice were more resistant to LPS-induced lung injury than were wild-type mice (23). Moreover, treatment with NOS2 inhibitors seems to prevent ALI in sheep after burn and smoke inhalation injury (35,36). On the other hand, there are reports suggesting a beneficial role of ·NO in ALI based on the following: (1 ) it downregulates the expression of adhesion molecules, resulting in a reduction in the migration and accumulation of neutrophils (37); (2 ) it inhibits cytokine production (38); and (3 ) in a clinical trial, as had been previously shown for some animal models (39), the use of NOS inhibitors in patients with sepsis resulted in an increase in mortality (40).…”

Section: Discussionmentioning

confidence: 99%

Effects of Acute Hypoxia and Lipopolysaccharide on Nitric Oxide Synthase-2 Expression in Acute Lung Injury

Agorreta

Garayoa²,

Montuenga³

et al. 2003

Am J Respir Crit Care Med

View full text Add to dashboard Cite

The potential role of nitric oxide synthase-2 (NOS2) in acute lung injury (ALI) has gained increasing attention. This study evaluates the effects of hypoxia, an important feature of ALI, on NOS2 expression in a rat model of ALI caused by exposure to hypoxia and LPS. Exposure to hypoxia alone had no effect on the expression of NOS2 in rat lungs. LPS treatment resulted in a significant increase in NOS2 in the lungs, which was further enhanced by concomitant exposure to hypoxia. Immunohistochemical analysis and in situ hybridization showed no changes in the expression of NOS2 in lung resident cells under any conditions. The increase in NOS2 levels is mainly due to the influx of NOS2-expressing inflammatory cells. By morphologic analysis, these inflammatory cells were identified as neutrophils, lymphocytes, and monocytes. In vitro experiments of lung epithelial and endothelial cell lines showed no detectable expression of NOS2 with any of the treatments. In a macrophage cell line, LPS-induced NOS2 expression was not affected by the concomitant exposure to hypoxia. In conclusion, LPS increases NOS2 expression in rat lungs through the recruitment of NOS2-producing leukocytes. Simultaneous exposure to LPS and hypoxia results in a greater influx of inflammatory cells that further enhances NOS2 expression.Keywords: acute respiratory distress syndrome; endotoxin; leukocytes; sepsis Nitric oxide (·NO) is a multifunctional, short-lived gas that may contribute to toxic free radical production and potentiate lung injury. ·NO is synthesized by a family of enzymes called nitric oxide synthases (NOS). There are three NOS isoforms, namely, NOS1 (neuronal NOS), NOS2 (inducible NOS), and NOS3 (endothelial NOS). These isoenzymes were first purified from rat brain (1), murine macrophages (2), and bovine aortic endothelial cells (3), respectively. NOS enzymes are classically classified as either constitutive (NOS1 and NOS3) or inducible (NOS2), although it is now known that the expression of NOS1 and NOS3 can be induced (4), and that NOS2 is constitutively expressed in numerous cell types (5). The so-called constitutive isoforms (NOS1 and NOS3) release low amounts of ·NO and their activity is dependent on calcium and calmodulin (6). On the other hand, NOS2 produces large amounts of ·NO after induction by stimuli such as endotoxin and inflammatory cytokines (7-9). All three isoenzymes have been found in the lung (10-12) and mediate a wide variety of biological events in the respiratory system, (Received in original form September 11, 2002; accepted in final form May 16, 2003) Supported by the Spanish Ministry of Health (FIS 00/0698 and RTIC C03/10) and the Fundació n Echébano.Correspondence and requests for reprints should be addressed to Javier J. Zulueta, M.D., Pulmonary Medicine Service, Clínica Universitaria de Navarra, University of Navarra, Avenida Pío XII, 36, 31008 Pamplona, Spain. E-mail: jzulueta@unav.es This article has an online supplement, which is accessible from this issue's table of contents online at www.atsjournals...

show abstract

“…Both N -nitro-L-arginine methyl ester (L-NAME), a nonselective NOS inhibitor, and aminoguanidine, a partially selective iNOS inhibitor, suppress increased vascular permeability of second-degree burned skin in mice (27). The partially selective iNOS inhibitor mercaptoethylguanidine (MEG) decreases pulmonary microvascular permeability changes in sheep after combined burn and smoke inhalation injury (26). N G -(1-iminoethyl)-L-lysine, a selective iNOS inhibitor, improves renal function in rats subjected to renal artery cross-clamping (22).…”

Section: Discussionmentioning

confidence: 99%

“…Recent publications report beneficial ef-fects of highly selective iNOS inhibitors on myocyte damage in acute cardiac allograft rejection (30), ischemia-reperfusion injury in skeletal muscle (35), and multiple organ dysfunction in hemorrhagic shock (17). Numerous studies with partially selective iNOS inhibitors support a role for iNOS and NO in thermal injury (26), but definitive data with highly selective iNOS inhibitors are lacking.…”

mentioning

confidence: 99%