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Specific mediator inhibition by the NO donors SNP and NCX 2057 in the peripheral lung: implications for allergen-induced bronchoconstriction.

Larsson Callerfelt, Anna-Karin LU ; Bäck, Magnus; Lundberg, Jon O and Dahlén, Sven-Erik (2009) In Respiratory Research 10(Jun 4).
Abstract
BACKGROUND: The aim of this study was to examine potential therapeutic effect of the two NO donors NCX 2057 (3-(4-hydroxy-3-methoxyphenyl)-2-propenoic acid) 4-(nitrooxy)butyl ester) and SNP (sodium nitroprusside) on the early allergic airway response in the peripheral lung. METHODS: The experiments were performed in guinea pig lung parenchyma (GPLP) derived from ovalbumin (OVA) sensitized guinea pigs. The effects of NCX 2057 and SNP were evaluated by contractile responses and mediator release during OVA challenge. The generation of nitrite and nitrate was assessed by chemiluminescence. Statistical analysis was evaluated by ANOVA. RESULTS: Cumulatively increasing concentrations of OVA (1-10,000 ng/ml) induced concentration-dependent... (More)
BACKGROUND: The aim of this study was to examine potential therapeutic effect of the two NO donors NCX 2057 (3-(4-hydroxy-3-methoxyphenyl)-2-propenoic acid) 4-(nitrooxy)butyl ester) and SNP (sodium nitroprusside) on the early allergic airway response in the peripheral lung. METHODS: The experiments were performed in guinea pig lung parenchyma (GPLP) derived from ovalbumin (OVA) sensitized guinea pigs. The effects of NCX 2057 and SNP were evaluated by contractile responses and mediator release during OVA challenge. The generation of nitrite and nitrate was assessed by chemiluminescence. Statistical analysis was evaluated by ANOVA. RESULTS: Cumulatively increasing concentrations of OVA (1-10,000 ng/ml) induced concentration-dependent contractions of the GPLP that were reduced by NCX 2057 (100 microM, p < 0.001) and SNP (100 microM, p < 0.05). Antigen-induced eicosanoid release was decreased by NCX 2057 (100 microM, p < 0.001) but not by SNP (100 microM), whereas the release of histamine was reduced by SNP (100 microM, p < 0.001) but not by NCX 2057 (100 microM). In addition, NCX 2057 (0.1-100 microM), but not SNP (0.1-100 microM), relaxed leukotriene D4 (10 nM) precontracted GPLP (p < 0.01). The guanylyl cyclase inhibitor ODQ had no effect on the NCX 2057 mediated relaxation. SNP released significantly less nitrite than NCX 2057. CONCLUSION: Although both SNP and NCX 2057 reduced the release of pro-inflammatory mediators, their profiles were distinctly different. Furthermore, NCX 2057 also induced smooth muscle dilation in the GPLP. The findings point to specific anti-inflammatory effects of different NO donors in the peripheral lung tissue. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Respiratory Research
volume
10
issue
Jun 4
publisher
BioMed Central
external identifiers
  • wos:000267320900001
  • pmid:19493362
  • scopus:70249141296
ISSN
1465-9921
DOI
10.1186/1465-9921-10-46
language
English
LU publication?
yes
id
3d11a0fa-1510-4880-90b8-f25b4d5de3b7 (old id 1434550)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19493362?dopt=Abstract
date added to LUP
2009-07-02 13:07:47
date last changed
2017-01-01 07:35:05
@article{3d11a0fa-1510-4880-90b8-f25b4d5de3b7,
  abstract     = {BACKGROUND: The aim of this study was to examine potential therapeutic effect of the two NO donors NCX 2057 (3-(4-hydroxy-3-methoxyphenyl)-2-propenoic acid) 4-(nitrooxy)butyl ester) and SNP (sodium nitroprusside) on the early allergic airway response in the peripheral lung. METHODS: The experiments were performed in guinea pig lung parenchyma (GPLP) derived from ovalbumin (OVA) sensitized guinea pigs. The effects of NCX 2057 and SNP were evaluated by contractile responses and mediator release during OVA challenge. The generation of nitrite and nitrate was assessed by chemiluminescence. Statistical analysis was evaluated by ANOVA. RESULTS: Cumulatively increasing concentrations of OVA (1-10,000 ng/ml) induced concentration-dependent contractions of the GPLP that were reduced by NCX 2057 (100 microM, p &lt; 0.001) and SNP (100 microM, p &lt; 0.05). Antigen-induced eicosanoid release was decreased by NCX 2057 (100 microM, p &lt; 0.001) but not by SNP (100 microM), whereas the release of histamine was reduced by SNP (100 microM, p &lt; 0.001) but not by NCX 2057 (100 microM). In addition, NCX 2057 (0.1-100 microM), but not SNP (0.1-100 microM), relaxed leukotriene D4 (10 nM) precontracted GPLP (p &lt; 0.01). The guanylyl cyclase inhibitor ODQ had no effect on the NCX 2057 mediated relaxation. SNP released significantly less nitrite than NCX 2057. CONCLUSION: Although both SNP and NCX 2057 reduced the release of pro-inflammatory mediators, their profiles were distinctly different. Furthermore, NCX 2057 also induced smooth muscle dilation in the GPLP. The findings point to specific anti-inflammatory effects of different NO donors in the peripheral lung tissue.},
  articleno    = {46},
  author       = {Larsson Callerfelt, Anna-Karin and Bäck, Magnus and Lundberg, Jon O and Dahlén, Sven-Erik},
  issn         = {1465-9921},
  language     = {eng},
  number       = {Jun 4},
  publisher    = {BioMed Central},
  series       = {Respiratory Research},
  title        = {Specific mediator inhibition by the NO donors SNP and NCX 2057 in the peripheral lung: implications for allergen-induced bronchoconstriction.},
  url          = {http://dx.doi.org/10.1186/1465-9921-10-46},
  volume       = {10},
  year         = {2009},
}