Nitric oxide regulatory role in sensitized guinea pig trachea (original) (raw)
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Possible functional modulation by acetylcholine of nitric oxide on guinea pig isolated trachea
Life sciences, 1998
The aim of this study was to evaluate whether acetylcholine induces NO release. We determined the responses on the cholinergic component of the response to electrical field stimulation (EFS) the effects of L-nitro-arginine-methyl-ester (L-NAME; 1 mM), an inhibitor of NO synthase, of L-Arginine (L-ARG; 1 mM), a precursor of NO synthesis, and methoctramine (0.01-0.1-1 microM), an antagonist of M2 receptors, alone or associated with L-NAME. The experiments were performed on guinea pig isolated intact- or denuded-epithelium tracheal rings contracted in a frequency-dependent manner to EFS. At the maximum frequency tested (30 Hz), the contractile response elicited was 60.36 +/- 0.61% of acetylcholine (100 microM) contraction, while the maximal relaxant effect induced by EFS was -28.40 +/- 0.61% in epithelium intact preparations. A pretreatment with L-NAME significantly (P<0.05) increased the contraction (76.08 +/- 1.39%) and reduced the relaxation elicited by EFS. L-NAME effect on both...
General physiology and biophysics, 2006
Nitric oxide (NO) is an important endogenous mediator involved in many biological functions in both physiological and pathological conditions. Many of studies suggest that high level of NO may play a role in the pathogenesis of various diseases including respiratory diseases with bronchial hyper-reactivity (BHR). The aim of our study was to examine the relationship between NO production and BHR. The reactivity of tracheal and lung tissue smooth muscle to histamine and acetylcholine was measured in vitro in male guinea pigs pre-treated with NO synthase (NOS) inhibitors. The drugs were administered in vivo during either 3 or 17 days. Furthermore, the animals were exposed in vivo to the toluene vapours after administration of agents. NOS inhibitors showed mainly beneficial effect in the presented study. They decreased the hyper-reactivity of the tracheal and lung tissue smooth muscle evoked by toluene. The decrease was dependent on the duration of their administration and on the type o...
British Journal of Pharmacology, 1998
Using a conscious, unrestrained guinea-pig model of allergic asthma, we investigated the role of endogenous nitric oxide (NO) in the regulation of airway (hyper)reactivity to histamine before and after the allergen-induced early and late asthmatic reactions, by examining the eect of inhalation of the NO synthase inhibitor N o-nitro-L-arginine methyl ester (L-NAME, 12 mM, 15 min) on the histamine-induced airway obstruction of ovalbumin-sensitized guinea-pigs before, and at 5.5 h and 23.5 h after allergen challenge. 2 Before allergen challenge, inhaled L-NAME caused a signi®cant 2.02+0.25 fold increase (P50.01) in airway reactivity to histamine; this eect was reversed within 2.5 to 6 h after administration. 3 After the allergen-induced early asthmatic reaction at 5 h after ovalbumin provocation, a signi®cant 3.73+0.67 fold increase (P50.01) of the airway reactivity to histamine was observed; subsequent inhalation of L-NAME at 5.5 h had no eect on the airway hyperreactivity, reassessed at 6 h. 4 After the late asthmatic reaction, at 23 h after ovalbumin provocation, a reduced, but still signi®cant airway hyperreactivity to histamine (2.18+0.40 fold; P50.05) was observed. Subsequent inhalation of L-NAME now signi®cantly potentiated the partially reduced airway hyperreactivity 1.57+0.19 fold (P50.05) to the level observed after the early asthmatic reaction. 5 When administered 30 min before allergen exposure, L-NAME signi®cantly enhanced the allergeninduced early asthmatic reaction. However, when administered at 5.5 h after allergen provocation, L-NAME did not aect the subsequent late asthmatic reaction. 6 These results indicate that endogenous NO is involved the regulation of histamine-and allergeninduced bronchoconstriction and that a de®ciency of cNOS-derived NO contributes to the allergeninduced airway hyperreactivity to histamine after the early asthmatic reaction, while a recovery of NO de®ciency may account for the partial reversal of the allergen-induced airway hyperreactivity after the late asthmatic reaction.
British Journal of Pharmacology, 2000
1 Cholinergic airway constriction is functionally antagonized by agonist-induced constitutive nitric oxide synthase (cNOS)-derived nitric oxide (NO). Since cNOS and arginase, which hydrolyzes Larginine to L-ornithine and urea, use L-arginine as a common substrate, competition between both enzymes for the substrate could be involved in the regulation of cholinergic airway reactivity. Using a perfused guinea-pig tracheal tube preparation, we investigated the modulation of methacholineinduced airway constriction by the recently developed, potent and speci®c arginase inhibitor N ohydroxy-nor-L-arginine (nor-NOHA).
The Protective Role of Epithelium-derived Nitric Oxide in Isolated Bovine Trachea
Pulmonary Pharmacology & Therapeutics, 2002
Airway epithelial cells from bovine airways can release relaxant factors such as nitric oxide (NO) and prostaglandin E 2 and the removal of airway epithelium results in an increased responsiveness of smooth muscle to spasmogen stimuli. In this study, we assessed whether or not epithelial NO modulates the contractile response of bovine trachea in vitro.
Divergent effects of Nitric oxide on airway epithelial cell activation
Biological Research, 2010
Nitric oxide (NO • ) is a gaseous mediator synthesized by nitric oxide sinthases. NO • is involved in the modulation of inflammation, but its role in airway inflammation remains controversial. We investigated the role of NO • in the synthesis of the chemokines Interleukin-8 and Monocyte Chemotactic Protein-1, and of Intercellular Adhesion Molecule-1 by human airway epithelial cells. Normal human bronchial epithelial cells and the bronchial epithelial cell line BEAS-2B were used. Ineterleukin-8 (IL-8) and Monocyte Chemotactic Protein-1 (MCP-1) secretion and Intercellular Adhesion Molecule-1 (ICAM-1) expression were measured by ELISA. mRNA was assessed by semiquantitative RT-PCR. Ineterleukin-8 secretion was significantly reduced after 24h incubation with the NO • donor, sodium nitroprusside. The effect was dose-dependent. Similar results were obtained with S-Nitroso-N-D,L-penicillamine and S-Nitroso-L-glutathione. Inhibition of endogenous NO • with the nitric oxide synthase inhibitor N-Nitro-L-arginine-methyl-esther caused an increase in IL-8 secretion by lypopolisaccharide-and cytokine-stimulated BEAS-2B cells. Sodium nitroprusside also caused a reduction in Monocyte Chemotactic Protein-1 secretion by both cell types. In contrast, Intercellular Adhesion Molecule-1 expression was upregulated by sodium nitroprusside. RT-PCR results indicate that the modulation of protein levels was paralleled by modification in mRNA levels. NO • has divergent effects on the synthesis of different inflammatory mediators in human bronchial epithelial cells.
Biochemical and Biophysical Research Communications, 1991
The interaction between parasympathetic and inhibitory non-adrenergic, non-cholinergic nerves in tracheal smooth muscle was investigated by determining the effects of the NOsynthase inhibitor L-No-nitro-ar inine (GNOARG) on contracttons and the associated acetylcholine release elicited by ield stimulation of the muscle. At frequencies above 2Hz P contractile responses to field stimulation were potentiated by L-NOARG (50pM). Qch motrypsin pre-treatment potentiated contractile responses at all frequencies, but the e B ects of LNOARG were unaltered. The effect of GNOARG on responses to 5Hz electrical stimulation was not mimicked by D-NOARG, was reversed by G, but not D-arginine and was unaffected by epithelium removal. LNOARG did not affect responses to exogenous acetylcholine nor the overflow of 3H from tissues previously loaded wtth [3H]-choline. It is therefore concluded that field stimulation of tracheal smooth muscle induces the release of an endogenous nitrate, which, by an inhibitory action on smooth muscle, functionally antagonises the concomitantly released parasympathetic neurotransmitter.
Journal of Pharmacology and Experimental Therapeutics, 2006
The effects of selective cyclooxygenase (COX) isoform (COX-1, COX-2) inhibition, alone or in combination with nitric-oxide synthase (NOS) blockade, on in vitro tracheal muscle responsiveness to histamine were investigated in healthy and ovalbumin (OVA)-sensitized guinea pigs. Immunohistochemistry showed that COX-1 and COX-2 are constitutively present in normal guinea pig trachea, particularly in the epithelial layer, and that COX-2 expression is enhanced in OVA-sensitized animals both in epithelial and subepithelial tissues. In normal guinea pigs, SC-560 [5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole] (COX-1 inhibitor) or DFU [5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furanone] (COX-2 inhibitor) significantly increased the contractile response to histamine, these effects being not additive. NOS inhibition by L-N G -nitro-arginine methyl ester (L-NAME) did not affect histamine-induced contraction but reversed the increase caused by COX-1 blockade while not modifying the enhancemethyl ester; PGI 2 , prostaglandin I 2 (prostacyclin); ANOVA, analysis of variance.
European Journal of Pharmacology, 2005
In the present study we investigated the lymphocytes infiltration and other parameters of allergic lung inflammation comparing mice submitted to acute suppression of nitric oxide synthesis with mice deficient in inducible nitric oxide synthase (NOS2 À/À ) gene. At weekly intervals C57Bl/6 mice, wild type and NOS2 À/À were sensitized twice with ovalbumin-alumen and challenged twice with ovalbumin aerosol and lungs examined 24 h later. In wild type mice, treatment with nitric oxide synthase inhibitor, N N -nitro-l-arginine-methyl-ester (l-NAME) or aminoguanidine (i.p., 30 min before each ovalbumin challenge) caused a significant decrease in bronchoalveolar lavage cell number: eosinophils (90%), lymphocytes NK1.1 + (70%), Tgy + (50%), CD4 + (55%), CD8 + (60%) and B220 + (65%). Both inhibitors abolished airway hyperreactivity and significantly reduced mucus secretion (l-NAME 64%; aminoguanidine 58%). Surprisingly, in NOS2 À/À mice these parameters of allergic lung inflammation were not significantly different when compared with wild type mice. In addition, treatment of NOS2 À/À mice with l-NAME or aminoguanidine did not affect these parameters. Thus, acute inhibition of NOS2 activity inhibits asthmalike responses but absence of NOS2 has no affect.