Inhibition of nitric oxide synthase reduces Sephadex-induced oedema formation in the rat lung: Dependence on intact adrenal function

Andersson, Sven; Källström, Leif; Malm, Monika G. K.; Miller‐Larsson, Anna; Axelsson, Bengt-Olof

doi:10.1007/bf01757698

Cited by 18 publications

(8 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We compared the effect of the nonselective NOS inhibitor, L-NAME, with the selective iNOS inhibitor, 1400W in a model of Sephadex-induced inflammation and found that L-NAME, and not 1400W, inhibit Sephadex-induced lung edema and lung tissue eosinophilia. This result is consistent with other workers who demonstrated that L-NAME reduced Sephadex-induced lung edema in the rat (Andersson et al, 1995) and inhibited antigen-induced airway microvascular permeability and eosinophilia in the guinea pig (Iijima et al, 1998) and eosinophilia in the sensitized and challenged rat (Ferreira et al, 1998). The studies described in this manuscript have taken these findings further by investigating the effects of a selective iNOS inhibitor 1400W, validating its activity in an LPS model of inflammation and testing its effectiveness in two models of eosinophilic lung inflammation.…”

Section: Discussionsupporting

confidence: 94%

Pharmacological Assessment of the Nitric-Oxide Synthase Isoform Involved in Eosinophilic Inflammation in a Rat Model of Sephadex-Induced Airway Inflammation

Birrell

McCluskie²,

Haddad³

et al. 2002

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Excessive local production of nitric oxide (NO) has been suggested to play a role in rodent models of airway inflammation and in pulmonary diseases such as asthma. However, even given the plethora of data available including gene expression data, pharmacological data, and gene deletion studies in animal models, it is still not clear which nitric-oxide synthase (NOS) isoform is involved in eosinophilic airway inflammation. In this rat study, the nonselective NOS inhibitor L-NAME (N G -nitro-L-arginine methyl ester), but not a selective inducible NOS (iNOS) inhibitor 1400W (N-3-(aminomethyl)benzyl)acetamidine), impacted on Sephadex-induced inflammation by significantly inhibiting lung edema, eosinophil infiltration, tumor necrosis factor ␣, interleukin-13, and eotaxin levels in the lung tissue. Furthermore, iNOS gene expression was not induced following Sephadex administration, which confirms that iNOS does not play a role in this model. To demonstrate that this phenomenon was not restricted to this model of asthma, L-NAME, but not 1400W, was shown to reduce eosinophilia in an antigen-induced model. However, in contrast to the Sephadex model, there was an induction of iNOS gene expression after antigen challenge. In a model of aerosolized lipopolysaccharide-induced inflammation, where iNOS gene expression is increased, 1400W inhibited the increased neutrophilia. These data suggest that the compound has been administered using an appropriate dosing regimen for iNOS inhibition in the rat lung. In conclusion, it appears that constitutive, not inducible, NOS isoforms are important in NO production in models of allergic inflammation, which questions whether there is a role for iNOS inhibitors as therapy for the treatment of asthma.

show abstract

Section: Discussionsupporting

confidence: 94%

Pharmacological Assessment of the Nitric-Oxide Synthase Isoform Involved in Eosinophilic Inflammation in a Rat Model of Sephadex-Induced Airway Inflammation

Birrell

McCluskie²,

Haddad³

et al. 2002

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…These doses were the same as those previously reported by TSUKAGOSHI et al [10] in the rat. Similarly, the differential effects of aminoguanidine and L-NAME at these doses were shown by ANDERSSON et al [28] in Sephadex-induced inflammation in the rat lung. The present results show both aminoguanidine and L-NMMA to inhibit allergen-induced inflammatory cell influx and increase epithelial permeability in sensitized animals 24 h after allergen challenge, whereas the cNOS inhibitors produce no effect.…”

Section: Discussionsupporting

confidence: 67%

Differential effects of nitric oxide synthase inhibitors in an <I>in vivo</I> allergic rat model

́¹,

Wale²,

Holt³

et al. 2000

European Respiratory Journal

View full text Add to dashboard Cite

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) inhibitorsv -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. Eur Respir J 2000; 15: 870±877.

show abstract

“…Inhibition of inducible nitric oxide synthase (iNOS) activity has been shown to have profound effect on edema formation in different models of inflammation [24]. Therefore, we think that, the first direction for future studies would be investigation of how exosomes affect COX2, PLA2, and iNOS signaling pathways at the site of acute inflammation.…”

Section: Discussionmentioning

confidence: 98%

Exosomes from Human Dental Pulp Stem Cells Suppress Carrageenan-Induced Acute Inflammation in Mice

et al. 2015

View full text Add to dashboard Cite

The primary goal of this study was to examine the effects of human dental pulp stem cell-derived exosomes on the carrageenan-induced acute inflammation in mice. Exosomes were purified by differential ultracentrifugation from the supernatants of stem cells derived from the dental pulp of human exfoliated deciduous teeth (SHEDs) cultivated in serum-free medium. At 1 h post-carrageenan injection, exosomes derived from supernatants of 2 × 10(6) SHEDs were administered by intraplantar injection to BALB/c mice; 30 mg/kg of prednisolone and phosphate-buffered saline (PBS) were used as positive and negative controls, respectively. Edema was measured at 6, 24, and 48 h after carrageenan injection. For the in vivo imaging experiments, AngioSPARK750, Cat B 750 FAST, and MMPSense 750 FAST were administered into the mouse tail vein 2 h post-carrageenan injection. Fluorescence images were acquired at 6, 24, and 48 h after edema induction by IVIS Spectrum in vivo imaging system. Exosomes significantly reduced the carrageenan-induced edema at all the time points studied (by 39.5, 41.6, and 25.6% at 6, 24, and 48 h after injection, respectively), to similar levels seen with the positive control (prednisolone). In vivo imaging experiments revealed that, both exosomes and prednisolone suppress activities of cathepsin B and matrix metalloproteinases (MMPs) at the site of carrageenan-induced acute inflammation, showing more prominent effects of prednisolone at the early stages, while exosomes exerted their suppressive effects gradually and at later time points. Our study demonstrates for the first time that exosomes derived from human dental pulp stem cells suppress carrageenan-induced acute inflammation in mice.

show abstract

Inhibition of nitric oxide synthase reduces Sephadex-induced oedema formation in the rat lung: Dependence on intact adrenal function

Cited by 18 publications

References 24 publications

Pharmacological Assessment of the Nitric-Oxide Synthase Isoform Involved in Eosinophilic Inflammation in a Rat Model of Sephadex-Induced Airway Inflammation

Pharmacological Assessment of the Nitric-Oxide Synthase Isoform Involved in Eosinophilic Inflammation in a Rat Model of Sephadex-Induced Airway Inflammation

Differential effects of nitric oxide synthase inhibitors in an <I>in vivo</I> allergic rat model

Exosomes from Human Dental Pulp Stem Cells Suppress Carrageenan-Induced Acute Inflammation in Mice

Contact Info

Product

Resources

About