Nitric oxide modulates eosinophil infiltration in antigen-induced airway inflammation in rats

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

“…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.…”

“…First, several studies have implicated a role for the iNOS isoform in allergic inflammation due to the increased gene expression seen following antigen challenge in animal models (Yeadon and Price, 1995;Liu et al, 1997) and the increased iNOS expression seen in diseased versus normal tissues in biopsy studies in man (Hamid et al, 1993). Second, pharmacological data exist, and there seems to be general agreement that nonselective NOS inhibitors reduce allergen-induced eosinophilia in several animal models (Feder et al, 1997;Ferreira et al, 1998;Iijima et al, 1998). However, the data incorporating the use of iNOS inhibitors are very confusing and often conflicting with many investigators using compounds with minimal selectivity for iNOS (Trifilieff et al, 2000), and several studies not demonstrating a dose-response relationship with the compounds used and not benchmarking their data by using nonselective NOS inhibitors (to rule out effects of compounds not due to NOS inhibition) (Koarai et al, 2000;Muijsers et al, 2001).…”

Effects of chronic l-NAME treatment lung tissue mechanics, eosinophilic and extracellular matrix responses induced by chronic pulmonary inflammation

“…NO effects in eosinophil recruitment are still a matter of controversy (26,27,28,33,34,6). Corroborating our findings, we previously showed that, in guinea pigs with chronic lung inflammation, eosinophilic airway recruitment was also not reduced by chronic L-NAME treatment (28).…”

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

“…The lack of effects of eNOS inhibition with L-NAME on cellular influx and vascular permeability in the present model was a surprising outcome and, since L-NAME has been shown to be 2,000 times more selective for eNOS than iNOS [24], these results would therefore suggest this isoenzyme to be selectively involved in the regulation of vascular tone and not in cell recruitment or plasma exudation. Furthermore, the present results are in agreement with recently published literature in rats suggesting L-NAME has no effect on the cellular migration at 6 or 24 h after allergen challenge [11]. However, in that study L-NAME was effective in abolishing the allergen-induced eosinophilia 48 h after allergen exposure.…”

“…In Brown Norway rats, aminoguanidine has been shown to increase IL-1b-induced bronchial responsiveness to bradykinin but not to acetylcholine, without having any effect on IL-1b-induced neutrophilia [10]. Further studies have demonstrated L-NAME to produce no effect on the total or differential cell count in sensitized rats 6 or 24 h following allergen challenge with ovalbumin (OVA) but to cause significant inhibition at 48 h [11]. Despite many studies, the role of NO in allergic inflammation is still unknown and the functional role of the different NOS isoenzymes remains controversial.…”