Differential effects of nitric oxide synthase inhibitors in an in vivo allergic rat model

Tulic, M.K., Wale, J.L., Holt, P.G. and Sly, P.D. (2000) Differential effects of nitric oxide synthase inhibitors in an in vivo allergic rat model. European Respiratory Journal, 15 5: 870-877. doi:10.1183/09031936.00.15587000

Author Tulic, M.K.
Wale, J.L.
Holt, P.G.
Sly, P.D.
Title Differential effects of nitric oxide synthase inhibitors in an in vivo allergic rat model
Journal name European Respiratory Journal   Check publisher's open access policy
ISSN 0903-1936
Publication date 2000-05
Sub-type Article (original research)
DOI 10.1183/09031936.00.15587000
Volume 15
Issue 5
Start page 870
End page 877
Total pages 8
Place of publication Lausanne, Switzerland
Publisher European Respiratory Society
Language eng
Formatted abstract
The in vivo role of nitric oxide in inflammatory cell migration, vascular permeability and the development of hyperresponsiveness to methacholine (MCh) was studied in rats 24h following ovalbumin (OVA) challenge. The NO synthase (NOS) inhibitors N(G)-mono-methyl-L-arginine (L- NMMA; nonselective), aminoguanidine (two-fold inducible NOS-selective), N(ω)-nitro-L-arginine methyl ester (L-NAME; 2000-fold endothelial cell NOS- selective) or S-methyl-L-thiocitrulline (100-fold neuronal NOS-selective) were administered (100 mg·kg-1 s.c.) to OVA-sensitized Piebald-Virol-Glaxo rats on 3 consecutive days during which they were challenged with allergen (1% OVA). Responses to inhaled MCh were measured in anaesthetized animals 24 h after OVA challenge. Cellular inflammation and vascular permeability were assessed using bronchoalveolar lavage (BAL) fluid collected 30 min after administration of Evans blue (50 mg·kg-1 i.v.). OVA challenge in sensitized animals induced hyperresponsiveness to MCh, inflammatory cell influx and increased leakage of Evans blue into the BAL fluid (n=9, p<0.001). Aminoguanidine was effective in inhibiting the allergen-induced cellular influx and microvascular leakage (n=9, p<0.001) without altering responses to MCh. This effect was reserved by L-arginine. L-NAME (n=5, p<0.01) and S- methyl-L-thiocitrulline (n=6, p<0.001) further potentiated the allergen- induced hyperresponsiveness without altering cellular inflammation. L-NMMA attenuated both the OVA-induced cellular influx and Evans blue leakage (n=8, p<0.001) as well as further potentiating the hyperresponsiveness to MCh (p<0.05). From these studies, it is suggested that, in allergic Piebald- Virol-Glaxo rats, nitric oxide production by inducible nitric oxide synthase plays a role in the migration of inflammatory cells and increase in vascular permeability following allergen challenge, whereas nitric oxide produced by the constitutively expressed neuronal nitric oxide synthase limits hyperresponsiveness to methacholine.
Keyword Allergic inflammation
Inducible nitric oxide synthase
Neuronal nitric oxide synthase
Nitric oxide synthase inhibitors
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Created: Wed, 17 Nov 2010, 11:54:50 EST