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


CONCLUSIONS
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.
Larsson
Anna-Karin
AK
Unit of Lung Biology, Division of Vascular and Respiratory Research, Department of Experimental Medical Science, Lund University, Lund, Sweden. Anna-Karin_L.Larsson@med.lu.se
Bäck
Magnus
M
Lundberg
Jon O
JO
Dahlén
Sven-Erik
SE
D000485:Allergens / Q000009:adverse effects*; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D002073:Butanes / Q000494:pharmacology*; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009566:Nitrates / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009573:Nitrites / Q000378:metabolism; D009574:Nitro Compounds / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D010047:Ovalbumin / Q000276:immunology
C484212:3-((4-hydroxy-3-methoxyphenyl)-2-propenoic acid 4-nitrooxy)butyl ester; D000485:Allergens; D002073:Butanes; D009566:Nitrates; D020030:Nitric Oxide Donors; D009573:Nitrites; D009574:Nitro Compounds; D009599:Nitroprusside; D010047:Ovalbumin