People complain about nasal stuffiness after SO2 exposure. This study was to investigate the acute effects of SO2 on nasal vascular and airway resistances in anaesthetized pigs for elucidating the underlying vascular and control mechanisms. Controlled ventilation was passed to the lungs or retrogradely through each nasal cavity. Nasal airway and lower airway pressures were measured to reflect airflow resistance changes. Systemic arterial pressure and nasal arterial flow were measured to calculate nasal vascular resistance. Nasal and pulmonary SO2 challenges were given. At 2 ppm, SO2 decreased systemic blood pressure and nasal vascular resistance but increased nasal airway and lower airway resistances. With increasing level to 8 ppm, SO2 increased systemic arterial pressure, nasal vascular and lower airway resistances but decreased nasal airway resistance. Nasal and pulmonary challenges induced similar responses. Ipsilateral nasal challenge elicited bilateral responses. Ruthenium red abolished the responses to nasal challenges. Bilateral vagosympathectomy eliminated the responses to lung challenges. Hence, SO2 at 2 ppm causes nasal congestion through sensory reflex vasodilatation but at higher levels nasal decongestion through sensory reflex vasoconstriction. Nasal congestion coupled with bronchoconstriction at levels of SO2 below short-term exposure limit (STEL) (≤ 2 ppm) would limit SO2 entering the lungs. Nasal decongestion at levels of SO2 beyond STEL (> 2 ppm) can effectively decrease total airway resistance as concurrent strong bronchoconstriction may impair ventilation.
Administration, Inhalation ; Airway Resistance ; drug effects ; Animals ; Lung ; drug effects ; Nasal Cavity ; drug effects ; Respiration ; Sulfur Dioxide ; pharmacology ; Swine ; Vascular Resistance ; drug effects ; Vasodilation

BACKGROUNDAirway hyperresponsiveness (AHR) is one of the most important characteristics of asthma. This study investigated the parameters, by which assess the airway responsiveness under tidal ventilation.

METHODSFemale BALB/c mice were sensitized and challenged with ovalbumin (OVA) (group A), and part of them were treated with budesonide aerosol (group B). All the mice were anaesthetized and mechanically ventilated. The values of tidal volume (Vt), airway pressure (PA), airway flow (F), expiratory lung resistance (RL) and dynamic compliance of the thorax and lung (CT-L) were recorded by the AniRes2003 animal lung function system. In addition, the expiratory volume in the first 0.1 second after the start of expiration (EV0.1) was obtained according to the flow-volume (F-V) curve. The maximal or minimal values of EV0.1, RL and CT-L were documented after each dose of methacholine (MCH) and compared with values from negative control group (group C).

RESULTS(1) When the dose of MCH reached 100 ng/g or 200 ng/g, the decrease of Vt in group A was much more significant than group C (P = 0.001, < 0.001 respectively), but not so between groups B and group C (P = 0.974, 0.362 respectively). (2) With the dose of 25, 50, 100 or 200 ng/g MCH, the decrease in percentage of EV0.1 in group A was much higher than group C (P = 0.012, 0.025, 0.001, 0.003 respectively), while that in group B showed no significant difference as compared with group C (P = 0.507, 0.896, 0.972, 0.785). (3) RL and CT-L: with the dose of 200 ng/g MCH, there was a statistically significant increase of RL in group A compared to group B or group C (P < 0.001, < 0.001 respectively), but no significant difference between groups B and C (P = 0.266). With doses of 100 ng/g and 200 ng/g MCH, there was a statistically significant decrease of CT-L in group A compared to group B (P = 0.001, = 0.001) and group C (P < 0.001, < 0.001 respectively), but no significant difference between groups B and C (P = 0.775, 0.310). (4) Histopathology: there were eosinophilic predominant peribronchial and perivascular inflammatory influx in murine lungs after OVA sensitizing and challenging, which could be counteracted by inhalation of budesonide in group B.

CONCLUSIONSThe decline in EV0.1 in response to MCH challenge correlated with simultaneous changes in Vt, RL and CT-L, but more sensitively than all the other parameters. The decline in EV0.1 and inflammation in murine lung could be significantly alleviated by inhalation of nebulized budesonide solution, which indicated that EV0.1 to MCH is a valid measure of AHR in mice.

Airway Resistance ; drug effects ; Animals ; Bronchial Hyperreactivity ; drug therapy ; Budesonide ; therapeutic use ; Female ; Lung Compliance ; drug effects ; Methacholine Chloride ; pharmacology ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; immunology

OBJECTIVETo investigate bronchial responsiveness to acetylcholine in allergic airway inflammation of SD rats.

METHODSSD rats were immunized and challenged by chicken ovalbumin (OVA). Airway responsiveness, acetylcholine (Ach) provocation concentration needed to increase baseline airway resistance by 200% (PC(200)) were measured.

RESULTSThe value of baseline airway resistance in asthma group was significantly higher than that in control group (2.282 +/- 0.128 vs 3.193 +/- 0.239; P < 0.01). After multiple ovalbumin exposures, airway responsiveness to intravenous injection of acetylcholine decreased significantly (-LogPC(200): 4.006 +/- 0.554 vs 2.059 +/- 0.262; P < 0.01). Bronchial alveolar lavage fluid (BALF) and lung tissue specimen analysis indicated that airway allergic inflammation was present.

CONCLUSIONSThe study demonstrates a dissociation between the bronchoconstrictor response and bronchial hyper-responsiveness and indicates that multiple ovalbumin exposures induces persistent bronchoconstriction with airway hypo-responsiveness despite airway allergic inflammation.

Acetylcholine ; pharmacology ; Airway Resistance ; Allergens ; immunology ; Animals ; Bronchi ; drug effects ; physiology ; Bronchial Hyperreactivity ; etiology ; Bronchoconstriction ; Lung ; pathology ; Male ; Ovalbumin ; immunology ; Rats ; Rats, Sprague-Dawley

AIM: Ma Huang Tang (Ephedra decoction, MHT) is a famous classical formula from Shang Han Lun by Zhang Zhongjing in the Han Dynasty. The anti-asthmatic effects of MHT and the possible mechanisms were tested. METHOD: An asthma model was established by ovalbumin (OVA)-induction in mice. A total of forty-eight mice were randomly assigned to six experimental groups: control, model, dexamethasone (2 mg·kg(-1)) and MHT (5, 10, and 20 mg·kg(-1)). Airway resistance (Raw) was measured by the forced oscillation technique, histological studies were evaluated by hematoxylin and eosin (HE) staining, Th1/Th2 and Th17 cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA), and Th17 cells were evaluated by flow cytometry (FCM). RESULTS: This study demonstrated that MHT inhibited OVA-induced increases in Raw and eosinophil count; interleukin (IL)-4 and IL-17 levels were recovered in bronchoalveolar lavage fluid, increased IFN-γ level in bronchoalveolar lavage fluid. Histological studies demonstrated that MHT substantially inhibited OVA-induced eosinophilia in lung tissue. Flow cytometry studies demonstrated that MHT substantially inhibited Th17 cells. CONCLUSION These findings suggest that MHT may effectively ameliorate the progression of asthma, and could be further investigated for potential use as a therapy for patients with allergic asthma.
Airway Resistance ; drug effects ; Animals ; Anti-Asthmatic Agents ; administration & dosage ; Asthma ; chemically induced ; drug therapy ; immunology ; physiopathology ; Cytokines ; immunology ; Down-Regulation ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; adverse effects ; Th1 Cells ; drug effects ; immunology ; Th17 Cells ; drug effects ; immunology ; Th2 Cells ; drug effects ; immunology

BACKGROUNDThe down-regulation of constitutive nitric oxide synthase (cNOS) and up-regulation of inducible nitric oxide synthase (iNOS) are associated with the allergen-provocated airway hyperresponsiveness (AHR). This study aimed to determine whether their alteration also plays an important role in the AHR induced by lipopolysaccharide (LPS).

METHODSHartley male guinea pigs, weighing between 250 g and 350 g, were injected with LPS at a dose of 1 mg/kg every 24 hours for three days. A non-selective NOS inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), or a selective inducible NOS inhibitor, aminoguanidine (AG), were used thirty minutes before each injection of LPS. Airway reactions, nitric oxide (NO) production and inflammatory changes were detected 24 hours after the last dose of LPS.

RESULTSAG significantly decreased the NO production in the bronchoalveolar lavage fluid (BALF) and sharply reduced the intensity of bronchoconstriction to histamine challenge. L-NAME also significantly decreased the NO production in the BALF, but had no effect on airway reactions or, perhaps, a tendency to enhance the intensity of AHR.

CONCLUSIONSThe data suggest that inducible NOS contributes to the AHR induced by repetitive intraperitoneal LPS, and constitutive NOS was also involved.

Airway Resistance ; drug effects ; Animals ; Bronchial Hyperreactivity ; chemically induced ; Enzyme Inhibitors ; pharmacology ; Guanidines ; pharmacology ; Guinea Pigs ; Lipopolysaccharides ; toxicity ; Male ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide ; biosynthesis ; Nitric Oxide Synthase ; antagonists & inhibitors ; physiology

AIMTo establish an antigen-specific asthmatic model of guinea pig induced by protein antigen extracted from Dermatophagoides farinae (Der f), and study the desensitization of dust mite drops (DMD, extracted from Der f) in a dose progressive manner and long-term sublingual administration.

METHODSTo sensitize the guinea pigs, the protein antigen emulsified in aluminium hydroxide gel was subcutaneously and intraperitoneally injected. To observe early-phase reaction of asthma, lung resistance (R(L)) and lung dynamic compliance (Cdyn) in the sensitized guinea pigs were determined by intravenously injecting antigen. To observe late-phase reaction of asthma, the sensitized guinea pigs were challenged with aerosolized antigen for 7 days. Subsequently, methacholine (Mch) in a cumulative dose-manner induced-airway hyperreactivity (AHR), inflammatory cells numbers in bronchoalveolar lavage fluid (BALF) and pathological changes of lung tissue were measured in the model. From the first day of sensitization, the guinea pigs in treatment group sublingually received DMD in a dose progressive manner. The model group sublingually received equivalent saline. The normal control group did not receive any treatment.

RESULTSThe guinea pigs in model group showed a significant increase in R(L) and decrease in Cdyn, and developed a marked AHR to Mch. The number of total leukocytes and eosinophils increased significantly in BALF. Serious infiltration of eosinophils was observed in pathological section of lung tissue. Compared with model group, DMD treatment group exhibited a significant amelioration for early-phase and late-phase reaction of asthma.

CONCLUSIONDMD in a dose progressive manner and long-term sublingual administration displays a significant desensitization on Der f antigen-specific asthmatic reaction. The results provided experimental evidence for clinical therapy.

Administration, Sublingual ; Airway Resistance ; drug effects ; Allergens ; immunology ; Animals ; Antigens, Dermatophagoides ; administration & dosage ; isolation & purification ; therapeutic use ; Asthma ; immunology ; physiopathology ; therapy ; Bronchoalveolar Lavage Fluid ; cytology ; Dermatophagoides farinae ; immunology ; Desensitization, Immunologic ; methods ; Eosinophils ; drug effects ; pathology ; Female ; Guinea Pigs ; Leukocyte Count ; Lung Compliance ; drug effects ; Male

AIMTo study cyclosporin A (CsA) aerosol for anti-airway hyperresponsiveness (AHR) in sensitized rats.

METHODSSensitized Sprague-Dawley rats were given cyclosporin A (5, 20 g.L-1) and sodium cromoglycate (SCG, 20 g.L-1) by aerosol (5 min per day), dexamethasone (DXM, 0.5 mg.kg-1) i.p. once per day for 7 d before antigen challenge. The respiratory resistance(R(aw)) and lung dynamic compliance(Cdyn) of the rats induced by methacholine (Mch) were measured 24 h after ovalbumin(OA) challenge. The PC50 changes of R(aw) and PC25 changes of Cdyn were also investigated.

RESULTSPretreatment with CsA, sodium cromoglycate and dexamethasone inhibited the increase of R(aw) and decrease of Cdyn caused by inhaling Mch. The value of R(aw) PC50 in the CsA(5 g.L-1) group 5.6 g.L-1, the CsA(20 g.L-1) group 6.4 g.L-1, the SCG group 8.3 g.L-1 and the DXM group 9.2 g.L-1, was significantly higher than that of the model group 1.9 g.L-1 (P < 0.05). The value of Cdyn PC25 in the CsA(5 g.L-1) group 4.3 g.L-1, the CsA(20 g.L-1) group 5.4 g.L-1, the SCG group 6.4 g.L-1 and the DXM group 6.2 g.L-1, was significantly higher than that of the model group 1.1 g.L-1 (P < 0.01).

CONCLUSIONAnti-AHR of CsA by aerosol in animal model offered an experimental evidence for topical inhalation of CsA in treatment of asthma.

Administration, Inhalation ; Aerosols ; Airway Resistance ; drug effects ; Animals ; Cyclosporine ; administration & dosage ; pharmacology ; therapeutic use ; Disease Models, Animal ; Female ; Immunosuppressive Agents ; administration & dosage ; pharmacology ; therapeutic use ; Lung Compliance ; drug effects ; Male ; Ovalbumin ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Respiratory Hypersensitivity ; chemically induced ; drug therapy

Reactive oxygen species (ROS) play a crucial role in acute lung injury. Tissue inflammation, the increased vascular permeability, and plasma exudation are cardinal features of acute lung injury. Angiopoietin-1 (Ang1) has potential therapeutic applications in preventing vascular leakage and also has beneficial effects in several inflammatory disorders. Recently developed COMP-Ang1 is more potent than native Ang1 in phosphorylating tyrosine kinase with immunoglobulin and EGF homology domain 2 receptor in endothelial cells. However, there are no data on effects and related molecular mechanisms of COMP- Ang1 on ROS-induced acute lung injury. We used hydrogen peroxide (H2O2)-inhaled mice to evaluate the effect of COMP-Ang1 on pulmonary inflammation, bronchial hyper-responsiveness, and vascular leakage in acute lung injury. The results have revealed that VEGF expression, the levels of IL-4, TNF-alpha, IL-1 beta, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in lungs, the levels of hypoxia-inducible factor-1alpha (HIF-1 alpha) and NF-kappa B in nuclear protein extracts, phosphorylation of Akt, and vascular permeability were increased after inhalation of H2O2 and that the administration of COMP-Ang1 markedly reduced airway hyper-responsiveness, pulmonary inflammation, plasma extravasation, and the increases of cytokines, adhesion molecules, and VEGF in lungs treated with H2O2. We have also found that the activation of HIF-1a and NF-kappa B and the increase of phosphoinositide 3-kinase activity in lung tissues after H2O2 inhalation were decreased by the administration of COMP-Ang1. These results suggest that COMP-Ang1 ameliorates ROS-induced acute lung injury through attenuating vascular leakage and modulating inflammatory mediators.
Acute Lung Injury/chemically induced/complications/*drug therapy/metabolism ; Administration, Inhalation ; Airway Resistance/drug effects ; Animals ; Bronchial Hyperreactivity/drug therapy/etiology ; Bronchoalveolar Lavage Fluid ; Capillary Permeability/*drug effects ; Cytokines/antagonists & inhibitors ; Female ; Hydrogen Peroxide/adverse effects ; Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors ; Intercellular Adhesion Molecule-1/metabolism ; Mice ; Mice, Inbred BALB C ; NF-kappa B/antagonists & inhibitors ; Pneumonia/*drug therapy/etiology ; Recombinant Fusion Proteins/*administration & dosage ; Vascular Cell Adhesion Molecule-1/metabolism