ovalbumin and Cough

Cough variant asthma (CVA) is a chronic inflammatory disease characterized by cough as the main symptom. Suhuang antitussive capsule (Suhuang), one of traditional Chinese patent medicines, mainly treats CVA clinically. Previous studies have shown that Suhuang significantly improved CVA, post-infectious cough (PIC), sputum obstruction and airway remodeling. However, the effect of Suhuang on ovalbumin-induced (OVA-induced) metabolic abnormalities in CVA is unknown.. This study aimed to identify potential metabolites associated with efficacy of Suhuang in the treatment of CVA, and determined how Suhuang regulates metabolites, and differential metabolites reduce inflammation and oxidative stress.. Rats were given 1 mg OVA/100 mg aluminum hydroxide in the 1st and 7th days by intraperitoneal injection and challenged by atomizing inhalation of 1% OVA saline solution after two weeks to establish the CVA model. Rats were intragastrically (i.g.) administrated with Suhuang at 1.4 g/kg and β-hydroxybutyric acid (β-HB) were given with different concentrations (87.5 and 175 mg/kg/day) by intraperitoneal injection for 2 weeks. After 26 days, GC-MS-based metabolomic approach was applied to observe metabolic changes and search differential metabolites. The number of coughs, coughs latencies, enzyme-linked immunosorbent assay (ELISA), histological analysis and quantitative-polymerase chain reaction (Q-PCR) were used to investigate the effects of Suhuang. Then β-HB on CVA rats, NLRP3 inflammasome and GSK3β/AMPK/Nrf2 signalling pathway were detected by western blotting.. The results showed that Suhuang treatment significantly enhanced the serum level of β-HB. Interestingly, exposure to exogenous β-HB was also protective against OVA-induced CVA. β-HB significantly reduced the number of coughs and lengthened coughs latencies, improved lung injury, reduced the secretion of various cytokines, and directly inhibited the NLRP3 inflammasome. In addition, β-HB increased the nuclear accumulation of Nrf2 by activating the GSK3β/AMPK signaling axis, and then inactivating the NF-κB signaling pathway, effectively protecting OVA-induced CVA from oxidative stress and inflammation.. The results of this study shows that β-HB can reduce inflammation and oxidative stress, the increased production of β-HB in serum might be the crucial factor for Suhuang to exert its effect in the treatment of CVA.

Topics: 3-Hydroxybutyric Acid; AMP-Activated Protein Kinases; Animals; Antitussive Agents; Asthma; Cough; Glycogen Synthase Kinase 3 beta; Inflammasomes; Inflammation; NF-E2-Related Factor 2; NLR Family, Pyrin Domain-Containing 3 Protein; Ovalbumin; Rats

Over the past 50 years, the prevalence of allergic respiratory diseases has been increasing. The Hygiene hypothesis explains this progression by the decrease in the bio-diversity of early microbial exposure. This study aims to evaluate the effect of early-life farm exposure on airway hyperresponsiveness and cough hypersensitivity in an allergic airway inflammation rabbit model.. A specific environment was applied to pregnant rabbits and their offspring until six weeks after birth. Rabbits were housed in a pathogen-free zone for the control group and a calf barn for the farm group. At the end of the specific environmental exposure, both groups were then housed in a conventional zone and then sensitized to ovalbumin. Ten days after sensitization, the rabbit pups received ovalbumin aerosols to provoke airway inflammation. Sensitization to ovalbumin was assessed by specific IgE assay. Cough sensitivity was assessed by mechanical stimulation of the trachea, and bronchial reactivity was assessed by methacholine challenge. The farm environment was characterized by endotoxin measurement.. A total of 38 rabbit pups were included (18 in the farm group). Endotoxin levels in the farm environment varied from 30 to 1854 EU.m-3. There was no significant difference in specific IgE values to ovalbumin (p = 0.826) between the two groups. The mechanical threshold to elicit a cough did not differ between the two groups (p = 0.492). There was no difference in the number of cough (p = 0.270) or the intensity of ventilatory responses (p = 0.735). After adjusting for age and weight, there was no difference in respiratory resistance before and after methacholine challenge.. Early exposure to the calf barn did not affect cough sensitivity or bronchial reactivity in ovalbumin-sensitized rabbits. These results suggest that not all farm environments protect against asthma and atopy. Continuous exposure to several sources of microbial diversity is probably needed.

Topics: Animals; Bronchi; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Cough; Dust; Endotoxins; Farms; Immunoglobulin E; Inflammation; Methacholine Chloride; Ovalbumin; Rabbits

Flavonol kaempferol possesses a broad spectrum of potent pharmacological activities that seem to be effective in the modulation of allergic respiratory diseases. In our study, an experimental animal model of ovalbumin (OVA)-induced allergic airway inflammation in guinea pigs was used to determine the anti-asthmatic potential of kaempferol. The parameters of specific airway resistance (sRaw) and cough reflex response were evaluated in vivo. In vitro, an assessment of tracheal smooth muscle (TSM) contractility and analyses of inflammatory cytokines (IL-4, IL-5, IL-13, GM-CSF, IFN-γ), transforming growth factor (TGF-β1), immune cells count and ciliary beating frequency (CBF) were performed. Both single (6, 20 mg/kg b. w. p. o.) and long-term administered doses of kaempferol (20 mg/kg b. w. p. o., 21 days) suppressed sRaw provoked by histamine in conscious animals. The administration of kaempferol for 21 days attenuated histamine-induced TSM contractility in vitro and ameliorated the progression of chronic airway inflammation by decreasing the levels of IL-5, IL-13, GM-CSF, eosinophil count in bronchoalveolar lavage (BAL) fluid and TGF-β1 protein level in lung tissue. Kaempferol also eliminated the alterations in cough reflex sensitivity invoked by OVA-sensitization, but it did not affect CBF. The results demonstrate that flavonol kaempferol can modulate allergic airway inflammation and associated asthma features (AHR, aberrant stimulation of cough reflex).

Topics: Airway Resistance; Animals; Anti-Asthmatic Agents; Bronchoalveolar Lavage Fluid; Bronchoconstriction; Cough; Cytokines; Disease Models, Animal; Guinea Pigs; Inflammation Mediators; Kaempferols; Leukocytes; Lung; Male; Ovalbumin; Pneumonia; Respiratory Hypersensitivity; Trachea; Transforming Growth Factor beta1

Hanchuan Zupa Granule (HCZP), a traditional Chinese ethnodrug, has the functions of supressing a cough, resolving phlegm, warming the lungs, and relieving asthma. In clinical practice employing traditional Chinese medicine (TCM), HCZP is commonly used to treat acute colds, cough and abnormal mucous asthma caused by a cold, or "Nai-Zi-Lai" in the Uygur language. Studies have confirmed the use of HCZP to treat cough variant asthma (CVA) and other respiratory diseases. However, the pharmacological mechanisms of HCZP remain unrevealed.. To investigate the anti-tussive and anti-asthmatic effects and the possible pharmacological mechanisms of HCZP in the treatment of CVA.. A guinea pig CVA animal model was established by intraperitoneal injection of ovalbumin (OVA) combined with intraperitoneal injection of aluminium hydroxide adjuvant and atomized OVA. Meanwhile, guinea pigs with CVA received oral HCZP (at dosages of 0.571, 0.285 and 0.143 g/kg bodyweight). The number of coughs induced by aerosol capsaicin was recorded, and the airway hyperresponsiveness (AHR) of CVA guinea pigs was detected with the FinePointe series RC system. H&E staining of lung tissues was performed to observe pathological changes. ELISA was used to detect inflammatory cytokines. qRT-PCR and western blotting analyses were used to detect the expression of Th1-specific transcription factor (T-bet), Th2-specific transcription factor (GATA3), and Toll-like receptor 4 (TLR4) signal transduction elements. These methods were performed to assess the protective effects and the potential mechanisms of HCZP on CVA.. Great changes were found in the CVA guinea pig model after HCZP treatment. The number of coughs induced by capsaicin in guinea pigs decreased, the body weights of guinea pigs increased, and inflammation of the eosinophilic airway and AHR were reduced simultaneously. These results indicate that HCZP has a significant protective effect on CVA. A pharmacological study of HCZP showed that the levels of interleukin-4 (IL-4) and IL-5 and tumour necrosis factor-α (TNF-α) in serum decreased. The amount of interferon-γ (IFN-γ) increased, mRNA and protein expression of TLR4 and GATA3 weakened, and mRNA and protein expression of T-bet increased.. HCZP ameliorated the symptoms of guinea pigs with CVA induced by OVA by regulating the Th1/Th2 imbalance and TLR4 receptors.

Topics: Animals; Anti-Asthmatic Agents; Antitussive Agents; Asthma; Body Weight; Capsaicin; Cough; Cytokines; Disease Models, Animal; Drugs, Chinese Herbal; Flavonoids; GATA3 Transcription Factor; Glycyrrhizic Acid; Guinea Pigs; Lung; Medicine, Chinese Traditional; Ovalbumin; Respiratory Hypersensitivity; T-Box Domain Proteins; Th1 Cells; Th2 Cells; Toll-Like Receptor 4; Triterpenes

This experimental study evaluated the anti-asthmatic capacity of the dihydroxyflavone chrysin in the settings of ovalbumin (OVA)-induced allergic inflammation.. The parameters that were used to assess the anti-asthmatic activity of chrysin included the specific airway resistance to histamine, the sensitivity to a chemically induced cough and the activity of chrysin on the ciliary beat frequency (CBF) of the respiratory epithelium. The anti-inflammatory potential was confirmed by the measurement of cytokine concentrations Th2 (IL-4, IL-5 and IL-13), Th1 (Granulocyte-macrophage colony-stimulating factor [GM-CSF], INF-γ and IL-12), leucocyte count in the bronchoalveolar lavage fluid (BALF) and growth factor TBF-β1 in lung homogenate.. Chronic administration of chrysin (30 mg/kg/day for 21 days) to OVA-sensitised guinea pigs showed bronchodilatory activity comparable to that of long-acting β 2 receptors agonist (LABA) salmeterol. Chrysin revealed antitussive efficiency but was not able to abolish the negative effect of OVA on CBF. Chrysin managed to ameliorate the progression of chronic airway inflammation by decreasing the count of eosinophils, lymphocytes and basophils, IL-5, L-13, GM-CSF, INF-γ in BALF, and TGF-β1 in lung homogenate.. The acquired results support the complex anti-asthmatic profile of chrysin. The flavone may represent an attractive compound for further studies concerning the prevention or treatment of asthma.

Topics: Animals; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Antitussive Agents; Asthma; Bronchoalveolar Lavage Fluid; Cough; Cytokines; Disease Models, Animal; Disease Progression; Flavonoids; Guinea Pigs; Inflammation; Male; Ovalbumin; Salmeterol Xinafoate

Chronic irritating cough in patients with allergic disorders may reflect behavioral or reflex response that is inappropriately matched to the stimulus present in the respiratory tract. Such dysregulated response is likely caused by sensory nerve damage driven by allergic mediators leading to cough hypersensitivity. Some indirect findings suggest that even acid-sensitive, capsaicin-insensitive A-δ fibers called "cough receptors" that are likely responsible for protective reflex cough may be modulated through immune driven inflammation. The aim of this study was to find out whether protective reflex cough is altered during acute allergic airway inflammation in rabbits sensitized to ovalbumin. In order to evaluate the effect of such inflammation exclusively on protective reflex cough, C-fiber mediated cough was silenced using general anesthesia. Cough provocation using citric acid inhalation and mechanical stimulation of trachea was realized in 16 ovalbumin (OVA) sensitized, anesthetized and tracheotomised rabbits 24h after OVA (OVA group, n = 9) or saline challenge (control group, n = 7). Number of coughs provoked by citric acid inhalation did not differ between OVA and control group (12,2 ±6,1 vs. 17,9 ± 6,9; p = 0.5). Allergic airway inflammation induced significant modulation of cough threshold (CT) to mechanical stimulus. Mechanically induced cough reflex in OVA group was either up-regulated (subgroup named "responders" CT: 50 msec (50-50); n = 5 p = 0.003) or down-regulated (subgroup named "non responders", CT: 1200 msec (1200-1200); n = 4 p = 0.001) when compared to control group (CT: 150 msec (75-525)). These results advocate that allergen may induce longer lasting changes of reflex cough pathway, leading to its up- or down-regulation. These findings may be of interest as they suggest that effective therapies for chronic cough in allergic patients should target sensitized component of both, reflex and behavioral cough.

Topics: Administration, Inhalation; Anesthesia; Animals; Bronchoalveolar Lavage Fluid; Citric Acid; Cough; Disease Models, Animal; Eosinophils; Female; Leukocyte Count; Male; Ovalbumin; Rabbits; Reflex; Respiratory Hypersensitivity

Topics: Animals; Antitussive Agents; Asthma; Capsules; Cough; Disease Models, Animal; Drugs, Chinese Herbal; Endoplasmic Reticulum Stress; Inflammasomes; Male; NLR Family, Pyrin Domain-Containing 3 Protein; Ovalbumin; Rats, Wistar; Respiratory Function Tests

BACKGROUND This study investigated the effects and underlying mechanisms of emodin on cough variant asthma (CVA) in mice. MATERIAL AND METHODS The bronchial asthma mouse model was successfully established by use of ovalbumin (OVA) sensitization and challenge. The BALB/c mice were divided into 6 groups: a control group, an OVA model without or with emodin (15, 30, 60 mg/kg) group, and a dexamethasone (0.5 mg/g) group. The effect of the treatment was determined by measuring airway responsiveness. The levels of immunoglobulin molecules, as well as inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and serum, were determined by ELISA. The lung tissues were stained by hematoxylin-eosin (HE). The expressions of Notch receptors (Notch 1-3) and Delta-like (DLL) 4 in the lung tissues were detected by RT-PCR and Western blot analysis. RESULTS Compared with the model group, emodin treatment significantly increased the levels of immunoglobulin E (IgE) and IgG1/IgG2a in BALF and serum (p<0.05). HE results indicated that emodin inhibited the infiltration of inflammatory cells and that emodin reduced the levels of inflammatory cytokines, interleukin (IL)-5, IL-17, and interferon (IFN)-γ in BALF and serum (p<0.05). Furthermore, the expressions of Notch 1, 2, 3, and DLL4 in lung tissue were inhibited by emodin treatment. CONCLUSIONS The results demonstrated that emodin alleviated inflammation in CVA mice, which might be associated with suppression of the Notch pathway. Emodin might be a promising therapeutic agent for allergic asthma.

Topics: Animals; Asthma; Bronchoalveolar Lavage Fluid; Cough; Cytokines; Disease Models, Animal; Emodin; Eosinophils; Immunoglobulin E; Immunoglobulin G; Inflammation; Lung; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Receptors, Notch

Cough is a major symptom of asthma frequently experienced during exercise but little is known about interactions between cough and exercise. The goal of our study was to clarify the potential modulation of the cough reflex (CR) by exercise in a spontaneously breathing anaesthetized animal model of airway eosinophilic inflammation.. Ten ovalbumin (OVA) sensitized adult rabbits and 8 controls were studied. The ventilatory response to direct tracheal stimulation, performed both at rest and during exercise was determined to quantify the incidence and the sensitivity of the CR. Broncho-alveolar lavages (BAL) and cell counts were performed to assess the level of the airway inflammation following OVA-induced sensitization. Exercise was mimicked by Electrically induced hindlimb Muscular Contractions (EMC).. Among 494 tracheal stimulations, 261 were performed at rest and 233 at exercise. OVA challenges in sensitized rabbits caused a significant increase in the percentage of eosinophils (p = 0.008) in BAL. EMC increased minute ventilation by 36% and 35% in OVA and control rabbits respectively, compared to rest values. The sensitivity of the CR decreased during exercise compared to baseline in control rabbits (p = 0.0313) while it remained unchanged in OVA rabbits.. The desensitization of the CR during exercise in control rabbits was abolished in OVA rabbits. The precise role of airway inflammation in this lack of CR desensitization needs to be further investigated but it might contribute to the exercise-induced cough in asthmatics.

Topics: Animals; Asthma; Cough; Desensitization, Immunologic; Muscle Contraction; Ovalbumin; Physical Exertion; Rabbits; Reflex

This study was designed to determine the effect of active sensitization with ovalbumin (Ova) on cough responses to inhaled irritant gases in mice. Conscious mice moved freely in a recording chamber, while the pressure change in the chamber and audio and video signals of the mouse movements were recorded simultaneously to measure the frequencies of cough reflex (CR) and expiration reflex (ER). To further verify the accuracy of cough analysis, the intrapleural pressure was also recorded by a telemetry sensor surgically implanted in the intrapleural space in a subgroup of mice. During the irritant gas inhalation challenge, sulfur dioxide (SO

Topics: Administration, Inhalation; Ammonia; Animals; Cough; Exhalation; Inhalation Exposure; Irritants; Lung Injury; Male; Mice; Mice, Inbred C57BL; Ovalbumin; Pneumonia; Reflex; Reflex, Abnormal; Sulfur Dioxide; Vehicle Emissions

The guinea pig sensitized by ovalbumin is the most widely used model to study cough experimentally, as the neurophysiology of the vagus nerve in the guinea pig is closest to humans. Nonetheless, the choice of the antigen remains questionable, which influences the translation of results into clinical medicine. The present study seeks to develop an alternative model of cough study using house dust mite sensitization (HDM). Thirty guinea pigs were divided into the HDM group, ovalbumin (OVA) group, and control group based on their cough response to 0.4 M citric acid. In the HDM group animals were sensitized by 0.25 %HDM aerosol, which they inhaled for 5 min over 5 days, followed by inhalation of 0.5 %HDM in the same protocol. Sensitization was confirmed by a skin test. Symptoms of allergic rhinitis were induced by intranasal application of 15 μl 0.5 %HDM and cough challenges with citric acid were performed. Airway resistance was measured in vivo by Pennock's method. We found that both HDM and OVA-sensitized groups showed a significantly enhanced nasal reactivity and cough response compared with controls. The airway resistance data did not show significant differences. We conclude that the HDM cough model replicates functional aspects of the OVA model, which may make it an alternative to the latter. However, the superiority of the HDM model for experimental cough studies remains to be further explored.

Topics: Airway Resistance; Animals; Citric Acid; Cough; Disease Models, Animal; Guinea Pigs; Immunization; Male; Ovalbumin; Pyroglyphidae; Respiratory Hypersensitivity; Skin Tests

Phosphodiesterases (PDEs) are enzymes involved in the degradation of cAMP and cGMP. Selective PDE4 inhibitors (e.g., roflumilast) are effective in therapy of chronic obstructive pulmonary disease associated with neutrophil inflammation. The aim of this study was to evaluate the effects of a selective PDE4 inhibitor, YM976, on citric acid-induced cough, in vivo and in vitro airway smooth muscle reactivity to histamine, and on inflammatory mediators in ovalbumin-sensitized guinea pigs, with experimentally induced eosinophil inflammation. The YM976 was administered intraperitoneally at a dose of 1.0 mg/kg once daily for 7 days. Sensitization with ovalbumin led to a significant increase in the number of coughs, and in vivo and in vitro airway reactivity. Also, increased plasma levels of IL-4, IL-5, and PAF were observed, with a significant increase in the differential count of eosinophils in both blood and bronchoalveolar lavage fluid. The YM976 suppressed the number of coughs, the airway reactivity in tracheal tissue strips, and the IL-4 level. The findings indicate that PDE4 inhibition by YM976 exerts antitussive and anti-inflammatory effects in guinea pigs with ovalbumin-induced eosinophilic inflammation.

Topics: Animals; Bronchial Hyperreactivity; Cough; Cyclic Nucleotide Phosphodiesterases, Type 4; Guinea Pigs; Male; Ovalbumin; Phosphodiesterase 4 Inhibitors; Pyridines; Pyrimidinones; Respiratory System

Expression of voltage-gated sodium channels (Nav) takes place in the airways and the role of Nav1.7 and Nav1.8 in the control of airway's defense reflexes has been confirmed. The activation of Nav channels is crucial for cough initiation and airway smooth muscle reactivity, but it is unknown whether these channels regulate ciliary beating. This study evaluated the involvement of Nav1.7 and Nav1.8 channels in the airway defense mechanisms using their pharmacological blockers in healthy guinea pigs and in the experimental allergic asthma model. Asthma was modeled by ovalbumin sensitization over a period of 21 days. Blockade of Nav1.7 channels significantly decreased airway smooth muscle reactivity in vivo, the number of cough efforts, and the cilia beat frequency in healthy animals. In the allergic asthma model, blockade of Nav1.8 efficiently relieved symptoms of asthma, without adversely affecting cilia beat frequency. The study demonstrates that Nav1.8 channel antagonism has a potential to alleviate cough and bronchial hyperreactivity in asthma.

Topics: Animals; Asthma; Cilia; Cough; Disease Models, Animal; Guinea Pigs; Hypersensitivity; Male; Muscle, Smooth; Ovalbumin; Respiratory Mucosa; Sodium Channel Blockers; Voltage-Gated Sodium Channels

Using an experimental model of allergic asthma, we evaluated the anti-asthmatic potential of polyphenol flavonol derivate morin after either acute or long-term treatment of male OVA-sensitised guinea pigs.. The following methods were used in experiments: the in-vitro tracheal smooth muscle contraction induced by histamine; the changes in specific airway resistance (sRaw) to histamine and the sensitivity of a chemically induced cough reflex both via an in-vivo method; the serum and BALF concentrations' analysis of the inflammatory cytokines interleukin IL-4, IL-5, IL-13; and lung tissue infiltration by eosinophils and mastocytes.. Our data show that acute morin (30 mg/kg) and chronic 21-day morin (30 mg/kg/day) administration had a comparable antitussive efficiency with opioid antitussive codeine. Acute morin bronchodilatory activity defined by in-vivo sRaw decline did not reach SABA salbutamol effect. However, bronchodilatory efficiency of morin after long-term administration was by 34% higher as effect of LABA salmeterol. The 21-day morin treatment of OVA-sensitised guinea pigs reduced the serum, BALF levels of IL-4 and IL-13, lung tissue eosinophil and mastocyte infiltration comparable with corticosteroid budesonide.. In summary, morin represents very rational target for additional studies as potential substance for control as well as prevention of asthma inflammation and symptoms.

Topics: Airway Resistance; Animals; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Antitussive Agents; Asthma; Bronchoalveolar Lavage Fluid; Bronchodilator Agents; Cough; Cytokines; Eosinophils; Flavonoids; Guinea Pigs; Histamine; Hypersensitivity; Inflammation; Lung; Male; Ovalbumin; Phytotherapy; Plant Extracts; Trachea

The aim of this study was to determinate bronchodilator, antitussive, and ciliomodulatory activity of inhaled combination therapy with budesonide and salmeterol, and to correlate the results with the anti-inflammatory effect. The experiments were performed using two models of allergic inflammation (21 and 28 days long sensitization with ovalbumine) in guinea pigs. The animals were treated daily by aerosols of budesonide (1 mM), salmeterol (0.17 mM), and a half-dose combination of the two drugs. Antitussive and bronchodilator activities were evaluated in vivo. The ciliary beat frequency (CBF) was assessed in vitro in tracheal brushed samples, and inflammatory cytokines (IL-4, IL-5, IL-13, GM-CSF, and TNF-α) were determined in bronchoalveolar lavage fluid (BALF). We found that the combination therapy significantly decreased the number of cough efforts, airway reactivity, and the level of inflammatory cytokines in both models of allergic asthma. Three weeks long sensitization led to an increase in CBF and all three therapeutic approaches have shown a ciliostimulatory effect in order: salmeterol < budesonid < combination therapy. Four weeks long ovalbumine sensitization, on the other hand, decreased the CBF, increased IL-5, and decreased IL-13. In this case, only the combination therapy was able to stimulate the CBF. We conclude that a half-dose combination therapy of budesonide and salmeterol shows comparable antitussive, bronchodilator, and the anti-inflammatory effect to a full dose therapy with budesonide alone, but had a more pronounced stimulatory effect on the CBF.

Topics: Animals; Asthma; Bronchodilator Agents; Budesonide; Cilia; Cough; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Guinea Pigs; Inflammation; Male; Ovalbumin; Salmeterol Xinafoate

The efficacy of H4R antagonist JNJ7777120 on nasal symptoms, cough, airway resistance (Raw), inflammatory cell count in bronchoalveolar lavage (BAL) and blood in ovalbumin (OVA) induced allergic rhinitis (AR) was studied in guinea pigs. Animals (n=8) were sensitized by i.p. OVA and were repeatedly challenged with nasal OVA to induce rhinitis, seven animals were not sensitized. Animals were pre-treated with JNJ7777120 2.5 and 5mg/kg i.p. 30 min prior OVA. Cough was induced by inhalation of citric acid, Raw was measured in vivo by Pennock's method as baseline, during AR and after JNJ7777120 treatment. Leucocyte count in BAL and blood was analyzed. JNJ7777120 (5mg/kg) significantly suppressed nasal symptoms and the number of coughs. This compound significantly inhibited airway reactivity to histamine, but not methacholine. Pre-treatment with JNJ7777120 5mg/kg did not influence significantly the leucocyte count in BAL and blood except for a significant decrease in monocyte count in blood compared to the control group (p<0.05). We conclude that the antitussive action of JNJ7777120 is peripheral. The primary effect of the compound is anti-inflammatory, and the suppression of cough is a consequence of reduced airway inflammation.

Topics: Airway Resistance; Aluminum Hydroxide; Animals; Bronchoalveolar Lavage Fluid; Citric Acid; Cough; Disease Models, Animal; Dose-Response Relationship, Drug; Guinea Pigs; Indoles; Inflammation; Injections, Intraperitoneal; Nose Diseases; Ovalbumin; Piperazines; Plethysmography; Serotonin Antagonists

Naringin, a well known component isolated from Exocarpium Citri Grandis, has significant antitussive effects. Recently, Naringin exhibited novel anti-inflammatory effect in chronic inflammatory diseases. In this work, we firstly evaluated the effects of naringin on enhanced cough, airway hyper-responsiveness (AHR), and airway inflammation in an ovalbumin-induced experimental cough-variant asthma (CVA) model in guinea pigs. We investigated the effect of naringin (18.4 mg/kg, per os, single dose or consecutively) on cough to inhaled capsaicin after challenge with an aerosolized antigen in actively sensitized guinea pigs. The effect of naringin on AHR to inhaled methacholine was evaluated 24 h after cough determination. Airway inflammation was assessed via bronchoalveolar lavage fluid (BALF) cytology and lung histopathology. Naringin, given consecutively, significantly reduced ovalbumin-induced enhanced cough and AHR, inhibited the increases in the leukocytes, interleukin-4 (IL-4), IL-5, and IL-13 in BALF compared with the model group. Moreover, the pathologic changes in lung tissues were clearly ameliorated by naringin treatment. These results suggest that naringin may be a beneficial agent for CVA treatment.

Topics: Animals; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Capsaicin; Cough; Disease Models, Animal; Flavanones; Guinea Pigs; Inflammation; Male; Ovalbumin

To evaluate the antiasthmatic and antitussive properties of the aqueous leaf extract of Bryophyllum pinnatum (B. pinnatum) (BP) Lam.. Ovalbumin-sensitized guinea pigs which were treated with BP for 21 consecutive days were exposed to 0.2% histamine aerosol in a glass chamber. Mucus viscosity, white blood cell and lymphocyte counts and tracheal wall morphometry were measured. Bouts of cough were counted pre and post acute exposure of extract-treated (× 7 d) guinea pigs to 7.5% citric acid aerosol in a chamber. Phenol red expectoration was estimated in mice after 7 d of daily administration of BP.. Doses of 200 and 400 mg/kg/day (×21 d) BP significantly increased the time for guinea pigs to experience preconvulsive dyspnoea. BP and salbutamol (0.5 mg/kg/day ×21 d) reduced mucus viscosity in the sensitized group to values comparable with controls. White blood cell, lymphocyte counts and tracheal morphometry were not significantly altered. Both doses of BP also significantly reduced the bouts of cough but only 400 mg/kg/day significantly inhibited the amount of phenol red secreted.. BP has demonstrated antiasthmatic and antitussive properties in these rodent models. These properties may underscore its use in Nigerian ethnomedicine.

Topics: Analysis of Variance; Animals; Anti-Asthmatic Agents; Antitussive Agents; Bronchial Spasm; Citric Acid; Cough; Female; Guinea Pigs; Histamine; Kalanchoe; Lung; Male; Mice; Mucus; Ovalbumin; Plant Extracts; Plant Leaves; Trachea; Viscosity

Among the pathogenic mechanisms of asthma, a role for oxidative/nitrosative stress has been well documented. Recent evidence suggests that histamine H₄ receptors play a modulatory role in allergic inflammation. Here we report the effects of compound JNJ 7777120 (JNJ), a selective H4 receptor antagonist, on antigen-induced airway inflammation, paying special attention to its effects on lipocortin-1 (LC-1/annexin-A1), a 37 kDA anti-inflammatory protein that plays a key role in the production of inflammatory mediators.. Ovalbumin (OA)-sensitized guinea pigs placed in a respiratory chamber were challenged with antigen. JNJ (5, 7.5 and 10 mg.kg⁻¹) was given i.p. for 4 days before antigen challenge. Respiratory parameters were recorded. Bronchoalveolar lavage (BAL) fluid was collected and lung specimens taken for further analyses 1 h after antigen challenge. In BAL fluid, levels of LC-1, PGD2 , LTB4 and TNF-α were measured. In lung tissue samples, myeloperoxidase, caspase-3 and Mn-superoxide dismutase activities and 8-hydroxy-2-deoxyguanosine levels were measured.. OA challenge decreased LC-1 levels in BAL fluid, induced cough, dyspnoea and bronchoconstriction and increased PGD2 , LTB4 and TNF-α levels in lung tissue. Treatment with JNJ dose-dependently increased levels of LC-1, reduced respiratory abnormalities and lowered levels of PGD2 , LTB4 and TNF-α in BAL fluid.. Antigen-induced asthma-like reactions in guinea pigs decreased levels of LC-1 and increased TNF-α and eicosanoid production. JNJ pretreatment reduced allergic asthmatic responses and airway inflammation, an effect associated with LC-1 up-regulation.

Topics: Animals; Annexin A1; Antigens; Asthma; Bronchoalveolar Lavage Fluid; Bronchoconstriction; Cough; Dose-Response Relationship, Drug; Guinea Pigs; Histamine Antagonists; Indoles; Inflammation; Lung; Male; Ovalbumin; Piperazines; Tumor Necrosis Factor-alpha; Up-Regulation

The aim of the study was to prepare and evaluate the experimental model of allergic asthma. Changes in chough reflex, bronchoconstriction and the degree of inflammation were studied in ovalbumin (OVA) sensitized guinea pigs after 0, 7, 14, 21 days of exposure. The cough reflex was induced by citric acid inhalation in conscious animals in a double chamber body plethysmograph. Tracheal smooth muscle reactivity was assessed by examining the in vitro response to histamine (H) (10(-8)-10(-3) mol/l) and in vivo to H nebulization (10(-6) mol/l). BALF levels of IL-4, IL-5 and the eosinophil count were used as parameters of airway inflammation. After 7 days of OVA sensitization, there was an increase in tracheal smooth muscle contractility in vitro to cumulative concentration of H and an increase in cough parameters. After 14 days of OVA sensitization, there was a further increase in tracheal smooth muscle contractility to H, an increase in airway resistance, and a small increase in cough parameters. After 21 day of OVA sensitization, cough parameters were significantly reduced, airway resistance after H inhalation was increased, and there were significant increases in IL-4, IL-5, and eosinophils in BALF. In conclusion, progress in asthmatic inflammation during 21-day OVA sensitization caused a gradual increase in inflammatory mediators, a decline in cough reflex, and enhanced bronchoconstriction. This experimental model of allergic asthma can be used for pharmacological modulations of defense reflexes and inflammation.

Topics: Airway Resistance; Animals; Asthma; Bronchoalveolar Lavage Fluid; Bronchoconstriction; Citric Acid; Cough; Disease Models, Animal; Eosinophils; Guinea Pigs; Histamine; Interleukin-4; Interleukin-5; Male; Muscle Contraction; Muscle, Smooth; Ovalbumin; Reflex; Trachea

Calcium release-activated calcium channels (CRAC) play unambiguous role in secretory functions of mast cells, T cells, and eosinophils. Less knowledge exists about the role of CRAC, widely distributed in airway smooth muscle (ASM) cells, in airway contractility. The presented study seeks to determine the possible participation of CRAC in ASM-based inflammatory airway disorders in guinea pigs. The acute and long-term administration (14 days) of the CRAC antagonist 3-fluoropyridine-4-carboxylic acid was used to examine the ASM contractility and associated reflexes in the guinea pig model of allergic airway inflammation by the following methods: (i) evaluation of specific airway resistance in vivo; (ii) evaluation of the contractile response of isolated ASM strips in vitro; and (iii) citric acid-induced cough reflex; (iv) measurement of exhaled NO levels (E(NO)). Allergic airway inflammation was induced by repetitive exposure of guinea pigs to ovalbumin (10(-6) M). The CRAC antagonist administered in a single dose to guinea pigs with confirmed allergic inflammation significantly reduced the cough response and the airway resistance, which corresponded with the findings in vitro. Long-term application of the CRAC antagonist had more strongly expressed effects. The results confirm the role of CRAC in the pathophysiology of experimental animal asthma and have a potential meaning for anti-asthma therapy.

Topics: Animals; Anti-Asthmatic Agents; Asthma; Calcium; Calcium Channel Blockers; Calcium Channels; Cough; Endoplasmic Reticulum; Eosinophils; Guinea Pigs; Humans; Hypersensitivity; Isonicotinic Acids; Male; Mast Cells; Muscle Contraction; Myocytes, Smooth Muscle; Nitric Oxide; Ovalbumin; Respiratory System; T-Lymphocytes

Phosphodiesterases (PDEs) are enzymes responsible for degradation of cAMP and cGMP in cells. Thus, PDE inhibitors may have significant clinical benefit in respiratory diseases associated with inflammation. The aim of the present study was to evaluate the effects of selective PDE4 (rolipram, ROL) and PDE7 inhibitors (BRL50481, BRL) on citric acid-induced cough, in vivo and in vitro airway smooth muscle reactivity in both healthy and ovalbumin sensitized guinea pigs. The drugs tested were administered intraperitoneally to male guinea pigs once daily for 7 days - ROL 1 mg/kg, BRL 1 mg/kg, and ROL+BRL 0.5 mg/kg. Double chamber whole body plethysmography was used for the evaluation of citric acid (0.6 M)-induced cough and specific airway resistance. An organ bath method was used for the measurement of tracheal and lung tissue strip contractions evoked by cumulative doses (10(-8)-10(-3) mol/L) of acetylcholine (ACH) and histamine (HIS). In healthy guinea pigs, the only significant relaxation was observed after ROL in ACH-induced contractions in vitro and the effect on cough was negligible. In ovalbumin-sensitized animals, more pronounced in vitro relaxing effects of BRL in HIS-induced contractions and of combination (ROL+BRL) in ACH-induced contractions were observed, with similar results in vivo, and no significant change in the number of cough efforts was observed in any of the groups tested. The results suggest that PDE4 and PDE7 inhibitors have stronger anti-inflammatory effects compared with direct effects on smooth muscle and cough, with a potential benefit of their concomitant administration.

Topics: Acetylcholine; Airway Resistance; Animals; Bronchial Hyperreactivity; Bronchoconstriction; Citric Acid; Cough; Cyclic Nucleotide Phosphodiesterases, Type 4; Cyclic Nucleotide Phosphodiesterases, Type 7; Guinea Pigs; Histamine; Male; Muscle Contraction; Muscle, Smooth; Ovalbumin; Phosphodiesterase 4 Inhibitors; Plethysmography, Whole Body; Respiratory System; Rolipram

In this study the effects of non-selective PDE inhibitors (theophylline and theobromine) and selective inhibitors of PDE 1, 3, 4 and 5 on cough, induced by citric acid, were evaluated. Inhalation of citric acid aerosol was used for cough provocation in healthy and ovalbumin-sensitized guinea pigs and the number of cough efforts was registered after visual and acoustic control by a skilled observer, with subsequent evaluation of airflow changes in a double chamber whole body plethysmograph. The pre-treatment with theophylline and theobromine (10 mg/kg b.w. intraperitoneally) decreased the number of cough efforts evoked by inhalation of citric acid aerosol (0.6 mol/l) in both healthy and ovalbumin-sensitized animals. The selective inhibitors (all 1 mg/kg b.w. intraperitoneally) of PDE1 (vinpocetin), PDE3 (cilostazol), and PDE4 (citalopram) showed antitussive effects in healthy guinea pigs. Conversely, the antitussive potential of PDE1 (vinpocetin), PDE4 (citalopram), and PDE5 (zaprinast) was observed in ovalbumin-sensitized animals. We conclude that the administration of non-selective PDE inhibitors influenced the citric acid-induced cough both in healthy and ovalbumin-sensitized guinea pigs, indicating the participation of a bronchodilating action and suppression of airway hyperreactivity in the cough suppression. With selective inhibitors, PDE4 inhibition seems to be the most effective in cough suppression, confirming its positive effects tested in chronic airway inflammatory diseases associated with bronchoconstriction and cough (Fig. 6, Ref. 27).

Topics: Animals; Antitussive Agents; Bronchial Hyperreactivity; Citric Acid; Cough; Guinea Pigs; Male; Ovalbumin; Phosphodiesterase Inhibitors; Reflex; Theobromine; Theophylline

The presented studies were aimed on experimental confirmation of Althaea officinalis polysaccharide rhamnogalacturonan antitussive effect and its changes in conditions of allergic inflammation.. We have tested whether rhamnogalacturonan inhibits cough reflex and modulates airways reactivity of guinea pigs in vivo. The cough in guinea pigs was induced by 0.3 M citric acid (CA) aerosol for 3 min interval, in which total number of cough efforts (sudden enhancement of expiratory flow accompanied by cough movement and sound) was counted. Specific airway resistance and its changes induced by citric acid aerosol were considered as an indicator of the in vivo reactivity changes.. 1) Althaea officinalis polysaccharide rhamnogalacturonan dose- dependently inhibits cough reflex in unsensitized guinea pigs. Simultaneously, plant polysaccharide shortened the duration of antitussive effect when it was been tested in inflammatory conditions. 2) Rhamnogalacturonan did not influence airways reactivity in vivo conditions expressed as specific resistance values neither sensitized nor unsensitized groups of animals. 3) The antitussive activity of codeine (dose 10 mg.kg(-1) b.w. orally) tested under the same condition was comparable to higher dose of rhamnogalacturonan in unsensitized animals. 4) The characteristic cellular pattern of allergic airways inflammation was confirmed by histopathological investigations.. Rhamnogalacturonan isolated from Althaea officinalis mucilage possesses very high cough suppressive effect in guinea pigs test system, which is shortened in conditions of experimentally induced airways allergic inflammation (Tab. 1, Fig. 4, Ref. 25). Full Text in free PDF www.bmj.sk.

Topics: Airway Resistance; Althaea; Animals; Antitussive Agents; Bronchial Hyperreactivity; Cough; Dose-Response Relationship, Drug; Guinea Pigs; Inflammation; Lung; Ovalbumin; Plant Extracts; Polysaccharides; Reflex; Trachea

Topics: Animals; Antigens; Asthma; Bronchial Hyperreactivity; Cough; Dyspnea; Guinea Pigs; Histamine Antagonists; Inflammation; Male; Ovalbumin; Receptors, G-Protein-Coupled; Receptors, Histamine; Receptors, Histamine H4; Respiratory Mucosa

Neurokinins are known to induce neurogenic inflammation related to respiratory diseases. The effects of CS-003 ([1-{2-[(2R)-(3,4-dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholin-2-yl]ethyl}spiro[benzo[c]thiophene-1(3H),4'-piperidine]-(2S)-oxide hydrochloride]), a novel triple neurokinin receptor antagonist, on several respiratory disease models were evaluated in guinea pigs. As we have already shown that CS-003 is intravenously effective, we first determined if CS-003 was orally effective. CS-003 dose-dependently inhibited substance P-induced tracheal vascular hyperpermeability, neurokinin A- and neurokinin B-induced bronchoconstriction with ID(50) values of 3.6, 1.3 and 0.89 mg/kg (p.o.), respectively. CS-003 (10 mg/kg, p.o.) inhibited the number of coughs induced by capsaicin aerosol (P<0.01) and the antitussive effect was comparable to that of codeine. CS-003 (10 mg/kg, p.o.) also inhibited airway hyperresponsiveness to methacholine chloride in ovalbumin-induced asthma models (P<0.01), a milder one and a severer one. On the other hand, montelukast (10 mg/kg, p.o.), a leukotriene receptor antagonist, significantly inhibited the hyperresponsiveness only in the milder model (P<0.05). In an ovalbumin-induced rhinitis model, oral administration of CS-003 inhibited nasal blockade in a dose-dependent manner and the inhibitory effect was comparable to that of dexamethasone (10 mg/kg, p.o.). CS-003 (i.v.) also dose-dependently inhibited cigarette smoke-induced bronchoconstriction, tracheal vascular hyperpermeability and mucus secretion. These data show that CS-003, a potent orally active triple neurokinin receptor antagonist, may be useful for the treatment of respiratory diseases associated with neurokinins, such as allergic asthma, allergic rhinitis, chronic obstructive pulmonary disease and cough.

Topics: Administration, Oral; Animals; Asthma; Bronchoconstriction; Capillary Permeability; Capsaicin; Cough; Cyclic S-Oxides; Disease Models, Animal; Guinea Pigs; Male; Morpholines; Mucus; Nicotiana; Ovalbumin; Pulmonary Disease, Chronic Obstructive; Receptors, Tachykinin; Respiratory Tract Diseases; Rhinitis; Smoke; Trachea

Increased cough reflex sensitivity is found in patients with allergic rhinitis and may contribute to cough caused by rhinitis. We have reported that cough to citric acid is enhanced in the guinea pig model of allergic rhinitis. Here we address the hypothesis that the cough reflex sensitivity is increased in this model. The data from our previous studies were analyzed for the cough reflex sensitivity. The allergic inflammation in the nose was induced by repeated intranasal instillations of ovalbumin in the ovalbumin-sensitized guinea pigs. Cough was induced by inhalation of doubling concentrations of citric acid (0.05-1.6 M). Cough threshold was defined as the lowest concentration of citric acid causing two coughs (C2, expressed as geometric mean [95% confidence interval]). We found that the cough threshold was reduced in animals with allergic rhinitis. C2 was 0.5 M [0.36-0.71 M] and 0.15 M [0.1-0.23 M] prior and after repeated intranasal instillations of ovalbumin, respectively, P<0.01, n=36). C2 was not affected in control animals (n=29). We have reported that the selective leukotriene cys-LT1 receptor antagonist montelukast inhibited cough enhancement in this model. We found that this was accompanied by inhibition of the changes in cough reflex sensitivity. C2 was reduced in animals with allergic rhinitis treated orally with vehicle (0.57 M [0.28-1.1] vs. 0.09 M [0.04-0.2 M], P<0.05, n=8), but not in animals treated with montelukast (0.57 M [0.22-1.4 M] vs. 0.52 M [0.17-1.6 M], NS, n=8). We conclude that the cough reflex sensitivity is increased in the guinea pig model of allergic rhinitis. Our results suggest that guinea pig is a suitable model for mechanistic studies of increased cough reflex sensitivity in rhinitis.

Topics: Acetates; Allergens; Animals; Anti-Asthmatic Agents; Citric Acid; Cough; Cyclopropanes; Guinea Pigs; Inflammation; Leukotriene Antagonists; Male; Nasal Mucosa; Ovalbumin; Quinolines; Reflex; Rhinitis, Allergic, Seasonal; Sulfides

As the administration of many antitussive drugs is often associated with adverse effects, new alternatives are evaluated in experimental and clinical conditions. The aim of this study was to assess the influence of selective inhibitors of PDE3 (cilostazol) and PDE4 (citalopram) on cough and airway reactivity. The number of cough efforts, specific airway resistance, in vitro airway reactivity, and differential blood cells count were measured in healthy and in ovalbumin-sensitized guinea pigs before and after administration of cilostazol or citalopram (1 mg/kg). Cilostazol significantly suppressed citric acid induced cough only in healthy guinea pigs, whereas citalopram in both healthy and ovalbumin-sensitized animals. Both PDE inhibitors decreased in vivo and in vitro airway reactivity to histamine and the count of monocytes and neutrophils, confirming their anti-inflammatory potential. Administration of selective PDE3 and PDE4 inhibitors may influence cough and airway reactivity in the model of ovalbumin-sensitized guinea pigs.

Topics: Animals; Antigens; Antitussive Agents; Blood Cell Count; Bronchial Hyperreactivity; Bronchoconstriction; Cilostazol; Citalopram; Cough; Guinea Pigs; Histamine Release; Leukocyte Count; Male; Ovalbumin; Phosphodiesterase 3 Inhibitors; Phosphodiesterase 4 Inhibitors; Phosphodiesterase Inhibitors; Tetrazoles

Cough variant asthma is known as a major cause of chronic cough. Fundamental features of cough variant asthma are prolonged non-productive cough responding to bronchodilator therapy, no history of wheezing or dyspnea attack, normal cough sensitivity and slightly increased bronchial responsiveness. Recently, we reported the animal model of cough variant asthma. The aim of this study was to clarify the involvement of cysteinyl leukotrienes (cysLTs) in this model by using a specific leukotriene receptor antagonist, montelukast. Cough number and specific airway resistance (sRaw) were measured during the antigen inhalation (1.5 min) and following 18.5 min, which was carried out 72 h after the first antigen inhalation in actively sensitized guinea pigs, and then total cell number and cell differentials in bronchoalveolar lavage fluid (BALF) were measured. Montelukast significantly reduced the antigen re-inhalation-induced cough, increase in sRaw, and increase in total cell number in BALF. In conclusion, cysLTs may play an important part in antigen-induced cough associated with bronchoconstriction and airway inflammation in cough variant asthma.

Topics: Acetates; Airway Resistance; Animals; Anti-Asthmatic Agents; Asthma; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Cough; Cyclopropanes; Disease Models, Animal; Guinea Pigs; Leukotrienes; Male; Ovalbumin; Quinolines; Sulfides

It is unclear whether inhaled lidocaine is effective against airway hyperreactivity and inflammation in asthma. The aim of this study was to investigate the effects of inhaled lidocaine on airway hyperreactivity and inflammation. Airway reactivity to inhaled histamine, cellular composition of bronchoalveolar lavage (BAL) fluid, plasma substance P (SP), and isolated lung tissue were evaluated in ovalbumin (OVA)-sensitized guinea pigs 7 days after OVA challenge. The effects of inhaled lidocaine on this model were also evaluated. Treatment with lidocaine was administered in two fashions: as single inhalation or inhalation bid for 7 consecutive days, for comparison with a saline-inhaled control group. Airway hyperreactivity to histamine, increase in number of total cells and increased proportion of eosinophils in BAL fluid, and marked eosinophil infiltration in airway walls were noted even 7 days after OVA challenge in the control group. Plasma SP level was also significantly increased. Although treatment with single lidocaine inhalation did not affect airway hyperreactivity, continued inhalation (bid for 7 days) attenuated airway hyperreactivity. Continued, but not single, inhalation of lidocaine also suppressed infiltration of eosinophils in BAL fluid and in airway walls. In addition, plasma SP levels were significantly reduced by continued but not by single inhalation. It appears possible that lidocaine when inhaled suppresses eosinophilic inflammation of the airway and SP-induced neurogenic inflammation, leading to alleviation of airway hyperreactivity.

Topics: Administration, Inhalation; Anesthetics, Local; Animals; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Capsaicin; Cell Count; Cough; Eosinophils; Guinea Pigs; Histamine; Inflammation; Lidocaine; Lung; Male; Ovalbumin; Substance P

Allergic rhinitis is one of the most common causes of chronic cough. The characteristic feature of allergic rhinitis is eosinophilic nasal inflammation. This study was determined to find the relation between airway eosinophils and chemically-induced cough in guinea pigs with antigen-induced rhinitis at the early and late allergic phases. Forty animals were sensitized with ovalbumin (OVA) and divided into four separated groups. Four weeks later, the sensitized animals were either once or repeatedly (6 times at 7-day intervals) intranasally challenged with OVA to develop experimental allergic rhinitis. The control group was given saline. Cough was elicited by inhalation of citric acid aerosols and evaluated at 30 min (early phase) or 24 h (late phase) after the 1st or 6th nasal challenge (NC) in the sensitized animals. The citric acid-induced cough was significantly increased in the sensitized animals in the early allergic phase after the first and repeated NC compared with the control values [14(9-19) vs. 16(10-17) vs. 8(6-10); P=0.049], whereas there was no significant increase in the cough response tested in the late allergic phase. A correlation between the cough intensity and the number of eosinophils from nasal mucosa only (P=0.008) was found.

Topics: Aerosols; Animals; Bronchi; Citric Acid; Cough; Disease Models, Animal; Eosinophilia; Guinea Pigs; Larynx; Lung; Mice; Nasal Mucosa; Ovalbumin; Pulmonary Eosinophilia; Rhinitis, Allergic, Perennial; Severity of Illness Index; Time Factors; Trachea

Stimulation of mechanoceptors is considered to be the major mechanism of cough. Our aim in this study was to evaluate the relationship between in vivo and in vitro airway reactivity (AR) in chemically- and antigen-induced airway hyperresponsiveness (AHR). AHR was induced chemically (toluene vapors) or via antigen (ovalbumin) in healthy guinea pigs. While toluene inhalation did not cause a significant difference in the number of cough efforts during citric acid nebulization, a significant increase in specific airway resistance after inhalation of histamine was observed, as measured in double chamber body plethysmograph. In contrast, ovalbumin led to a significant increase in both the number of cough efforts and in vivo AR. The in vitro tests confirmed the presence of increased reactivity of tracheal and lung tissue strips to histamine. However, no clear correlation between bronchoconstriction and cough reflex was found in the experimental model used for this study.

Topics: Airway Resistance; Animals; Bronchial Provocation Tests; Bronchoconstriction; Bronchoconstrictor Agents; Citric Acid; Cough; Disease Models, Animal; Dose-Response Relationship, Drug; Guinea Pigs; Histamine; Lung; Male; Ovalbumin; Reflex; Respiratory Hypersensitivity; Toluene; Trachea

Cough is a common and important symptom of asthma and allergic rhinitis. Previous experimental evidence has shown enhanced cough sensitivity during early phase of experimental allergic rhinitis in guinea pigs. We hypothesized that airway inflammation during the late phase response after repeated nasal antigen challenge may affect the afferent sensory nerve endings in the larynx and tracheobronchial tree and may also modulate cough response. In the present study we evaluated the cough sensitivity during a period of early and late allergic response in sensitized guinea pigs after repeated nasal antigen challenges. Forty-five guinea pigs were sensitized with ovalbumin (OVA). Four weeks later 0.015 ml of 0.5 % OVA was intranasally instilled to develop a model of allergic rhinitis that was evaluated from the occurrence of typical clinical symptoms. Animals were repeatedly intranasally challenged either by OVA (experimental group) or by saline (controls) in 7-day intervals for nine weeks. Cough was elicited by inhalation of citric acid aerosols. Cough was evaluated at 1 or 3 h after the 6th nasal challenge and 17 or 24 h after the 9th nasal challenge. The cough reflex was significantly increased at 1 and 3 h after repeated nasal challenge in contrast to cough responses evoked at 17 and 24 h after repeated nasal challenge. In conclusion, enhanced cough sensitivity only corresponds to an early allergic response after repeated nasal challenges.

Topics: Allergens; Animals; Citric Acid; Cough; Disease Models, Animal; Guinea Pigs; Immunization; Male; Nasal Provocation Tests; Ovalbumin; Respiratory System; Rhinitis, Allergic, Perennial; Sneezing; Time Factors

Gastrooesophageal reflux (GER) is a frequent cause of chronic cough. Several investigators have indicated that inhibitors of H(+)K(+)ATPase (proton pump inhibitors; PPIs) could relieve coughing via inhibition of acid reflux. However, we considered that PPIs might directly inhibit increased cough reflex sensitivity.. The present study was designed to examine whether PPIs directly inhibit antigen-induced increase in cough reflex sensitivity and to elucidate the mechanism.. Actively sensitized guinea-pigs were challenged with aerosol antigen (ovalbumin, OVA) and cough reflex sensitivity to inhaled capsaicin was measured 24 h later. The PPIs (omeprazole and rabeprazole) or the histamine H(2) blocker cimetidine were administered intraperitoneally 1 h before OVA challenge and before measuring cough reflex sensitivity, then bronchoalveolar lavage fluid (BALF) was immediately collected. The pH of the fluid obtained by bronchial washing was determined after examining the effect of rabeprazole on the cough response to capsaicin.. The number of coughs elicited by capsaicin was significantly increased 24 h after challenge with OVA compared with saline, indicating antigen-induced increase in cough reflex sensitivity. Both PPIs dose dependently and significantly inhibited antigen-induced cough hypersensitivity. Omeprazole did not influence the antigen-induced increase in the total number of cells or ratio (%) of eosinophils in BALF. Cimetidine did not affect the antigen-induced cough hypersensitivity or cellular components of BALF. The pH of the bronchial washing fluid was significantly decreased in antigen-challenged animals. Rabeprazole did not affect the antigen-induced decrease in the pH of bronchial washing fluid.. These findings show that PPIs, but not histamine H(2) blockers, can directly decrease antigen-induced cough reflex hypersensitivity, while the mechanism remains unclear.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Allergens; Animals; Benzimidazoles; Bronchi; Bronchoalveolar Lavage Fluid; Capsaicin; Cimetidine; Cough; Dose-Response Relationship, Drug; Guinea Pigs; H(+)-K(+)-Exchanging ATPase; Histamine H2 Antagonists; Hydrogen-Ion Concentration; Immunohistochemistry; Irritants; Omeprazole; Ovalbumin; Proton Pump Inhibitors; Rabeprazole; Trachea

To observe the effect on infantile allergic cough with Minkeqing oral liquid (Minkeqing) and to study its cell molecular biologic mechanism.. The rat model was induced by inhalating ovalbumin; then the effects of Minkeqing on IL-6, IL-8, ET-1, TX-B2 in the blood and the bronchoalveolar lavage fluid (BALF) of the animal model were observed.. Minkeqing could reduce the levels of IL-6,IL-8,ET-1,Tx-B2 in the blood and BALF of the animal model.. Minkeqing has the significant function of inhibiting the release of inflammatory mediums.

Topics: Animals; Bronchoalveolar Lavage Fluid; Cough; Drug Combinations; Drugs, Chinese Herbal; Endothelin-1; Hypersensitivity; Interleukin-6; Interleukin-8; Male; Ovalbumin; Plants, Medicinal; Random Allocation; Rats; Rats, Wistar; Thromboxane B2

Experimental allergic rhinitis produces enhanced cough response in awake guinea pigs. Leukotriene receptor antagonists, as anti-inflammatory agents, have been effective in treatment of asthma and allergic rhinitis to inhibit the early and late allergic response. In the present study, we evaluated the effect of montelukast (Singulair, Merck, USA) on the cough reflex in an experimental model of allergen-induced rhinitis in guinea pigs. Guinea pigs (n=16) were sensitized with intraperitoneal ovalbumin (OVA). The animals were then used to develop a model of allergic rhinitis by repeated intranasal instillation of 0.5% OVA at weekly intervals for 8 weeks. Allergic rhinitis was evaluated from the occurrence of typical clinical symptoms including sneezing, conjunctival and nasal secretion, or nasal acoustic phenomenon. Between the 6(th) and 8(th) nasal challenge (NCh) the animals (n=8) were treated daily for 14 days with oral montelukast (10mg/kg). Cough was induced by citric acid aerosol inhalation in gradually increasing concentration (0.05-1.6 M) and was evaluated before sensitization and then after the 1(st), 6(th), and 8(th) nasal challenge when rhinitis symptoms were most conspicuous. The intensity of cough was significantly increased after the first and repeated nasal OVA challenges, and reduced after the 8(th) NCh that was preceded with montelukast treatment [9(6-14) vs. 16.5(14-22) vs. 25.5(23-42) vs. 8.5(8-13); P=0.0003]. We conclude that antileukotriene therapy suppresses the stimulating effect of experimental allergic rhinitis on the chemically-induced cough in awake guinea pigs.

Topics: Acetates; Administration, Oral; Animals; Citric Acid; Cough; Cyclopropanes; Disease Models, Animal; Guinea Pigs; Laryngeal Mucosa; Leukotriene Antagonists; Male; Membrane Proteins; Ovalbumin; Quinolines; Receptors, Leukotriene; Rhinitis, Allergic, Perennial; Sulfides; Time Factors

This study evaluates the effects of a copper amine oxidase (histaminase) purified from the pea seedling as a free or immobilized enzyme on asthmalike reactions to inhaled antigen in actively sensitized guinea pig in vivo. Male albino guinea pigs, sensitized with ovalbumin, were challenged with the antigen given by aerosol; free histaminase or CNBr-Sepharose immobilized histaminase was given intraperitoneally (20 microg, 3 or 24 h before antigen challenge) or by aerosol (4 microg, 30 min before or during ovalbumin aerosol). The following parameters were examined: latency time for the onset of respiratory abnormalities, cough severity score, and occurrence and duration of dyspnea. We also evaluated lung histopathology, mast cell degranulation, and lung myeloperoxidase and malonydialdehyde levels. Histaminase significantly reduced the severity of cough and the occurrence of dyspnea and delayed the onset of respiratory abnormalities. Both enzymes prevented bronchial constriction, pulmonary air space inflation, leukocyte infiltration (evaluated as myeloperoxidase activity), and lipoperoxidation of cell membranes (evaluated as malonyldialdehyde production). No relevant differences in pharmacological potency were noted between free or immobilized enzyme. This study provides evidence that histaminase counteracts acute allergic asthmalike reaction in actively sensitized guinea pigs, raising the possibility of new therapeutic strategies for allergic asthma in humans.

Topics: Administration, Inhalation; Aerosols; Amine Oxidase (Copper-Containing); Animals; Antigens; Asthma; Cough; Enzymes, Immobilized; Guinea Pigs; Immunization; Injections, Intraperitoneal; Lung; Male; Ovalbumin; Pisum sativum; Respiratory Function Tests; Respiratory Hypersensitivity; Seedlings

There is currently considerable interest in the potential value of selective inhibitors of cyclic nucleotide phosphodiesterase 4 in the treatment of asthma. However, whether they influence eosinophilic airway inflammation-associated cough remains unclear. The objective of this study was to investigate the effects of selective phosphodiesterase 4 inhibitor SB207499 on cough response and airway inflammation in guinea pigs sensitized and challenged with ovalbumin.. Forty sensitized guinea pigs were randomly divided into four groups: control (n = 10), challenge (n = 10), SB207499 (n = 10) and aminophylline (n = 10), then challenged with aerosol of 1% ovalbumin or saline. Two hours later, animals were intraperitoneally injected with either saline, 25 mg/kg of SB207499 or aminophylline. At the 24th hour, the injection was repeated with 2.5 mg/kg and 25 mg/kg SB207499 or aminophylline, then cough response to inhaled capsaicin and airway responsiveness to methacholine inducing a 150% of the peak airway pressure to the baseline (PC150) was measured. Finally, total cell number and differentials in bronchoalveolar lavage fluid were analysed.. The cough frequency per 3 minutes and PC150 in the challenge group were (22 +/- 4) times/3 minutes and (198 +/- 54) microg/ml, which were significantly different from (6 +/- 2) times/3 minutes and (691 +/- 81) microg/ml in the control group (P < 0.05, respectively). The injection of 25 mg/kg SB207499 significantly inhibited the increased cough response and airway hyperresponsiveness, the cough frequency and PC150 in guinea pigs were (13 +/- 2) times/3 minutes and (680 +/- 81) microg/ml (P < 0.05), which differed significantly from (18 +/- 2) times/3 minutes and (400 +/- 86) microg/ml after the administration of the same dose of aminophylline (P < 0.05). The inhibition of SB207499 on cough response was dose-dependent. Similarly, SB207499 decreased the total cell number and percentage of eosinophils in bronchoalveolar lavage fluid to (2.1 +/- 0.5) x 10(6)/ml and (20 +/- 5)% respectively, which were significantly different from (3.2 +/- 0.5) x 10(6)/ml and (29 +/- 5)% in the aminophylline group (P < 0.05, respectively) or (4.2 +/- 0.7) x 10(6)/ml and (35 +/- 4)% in the challenge group (P < 0.05, respectively).. Phosphodiesterase 4 inhibitor may be more useful than aminophylline for cough associated with eosinophilic airway inflammation via inhibiting airway inflammation and airway hyperresponsiveness.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Animals; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Cough; Cyclic AMP; Cyclic Nucleotide Phosphodiesterases, Type 4; Cyclohexanecarboxylic Acids; Dose-Response Relationship, Drug; Guinea Pigs; Male; Nitriles; Ovalbumin; Phosphodiesterase Inhibitors

Allergic rhinitis is a common cause of chronic cough. Topical corticosteroids are regarded as the most effective first-time treatment in allergic rhinitis. In this study we evaluated the cough sensitivity during the early and late allergic responses in guinea pigs with experimental allergic rhinitis. Another aim of the study was to follow up the effect of inhaled beclomethasone dipropionate on the cough in guinea pigs with allergic rhinitis. 31 guinea pigs were sensitized with ovalbumin (OA). Animals were intranasally challenged with OA (experiment) or saline (control) in 7-day intervals for 9 weeks. Cough was induced by inhalation of citric acid aerosols in gradually increasing concentrations for 30 s and was evaluated 1 h after the 8(th) nasal challenge (NCH) and 17 h after the 9(th) NCH. Cough was significantly increased only during an early allergic response, 1 h after repeated NCH [18 (14-23) vs. 8 (3-10); P<0.001]. Five experimental animals were inhaling aerosol of beclomethasone dipropionate seven days between the 8(th) and the 9(th) NCH and cough was evaluated 1 h after the 9(th) NCH. Inhaled corticosteroids significantly inhibited the enhanced allergic rhinitis related cough [4 (1-9) vs.19 (9-37) vs. 6 (3-9); P<0.05].

Topics: Administration, Inhalation; Aerosols; Animals; Anti-Inflammatory Agents; Beclomethasone; Bronchial Provocation Tests; Citric Acid; Cough; Guinea Pigs; Male; Ovalbumin; Rhinitis

Cough variant asthma is known as a major cause of chronic cough. Fundamental features of cough variant asthma are prolonged nonproductive cough responding to bronchodilator therapy, no history of wheezing or dyspnea attack, normal cough sensitivity, and slightly increased bronchial responsiveness. Animal model of cough variant asthma has not been reported. The aim of this study was to establish an animal model for studying detailed pathophysiology of cough variant asthma. Bronchial responsiveness to methacholine and cough reflex sensitivity to capsaicin were measured 72 hours after antigen (ovalbumin, OA) inhalation in actively sensitized guinea pigs. Next, cough number and specific airway resistance (sRaw) were measured during 20 minutes following reinhalation of OA solution, which was carried out 72 hours after the first OA inhalation, and then total cell number and cell differentials in bronchoalveolar lavage fluid (BALE) were measured. Bronchial responsiveness to methacholine, but not cough reflex sensitivity to capsaicin, was significantly increased 72 hours after the first inhalation of OA solution. Number of coughs, sRaw and total cell number in BALF increased significantly by the OA reinhalation, and the cough number and the increase in sRaw were significantly suppressed by beta2 agonist, procaterol. FK224, a specific neurokinin (NK) receptor antagonist, did not significantly influence the OA reinhalation-induced cough and increase in sRaw and total cell number in BALF in this model In conclusion, pathophysiologic feature of this animal model is similar to that of clinical cough variant asthma. Tachykinins may not play an important part in antigen-induced cough associated with bronchoconstriction and airway inflammation in cough variant asthma.

Topics: Airway Resistance; Allergens; Animals; Asthma; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Bronchoconstriction; Bronchodilator Agents; Capsaicin; Cough; Disease Models, Animal; Guinea Pigs; Male; Methacholine Chloride; Ovalbumin; Peptides, Cyclic; Procaterol; Tachykinins

Toxic influence of high oxygen concentration on pulmonary function and structures has been known for many years. However, the influence of high oxygen concentration breathing on defensive respiratory reflexes is still not clear. In our previous experiments, we found an inhibitory effect of 100 % oxygen breathing on cough reflex intensity in healthy guinea pigs. The present study was designed to detect the effects of hyperoxia on cough reflex in guinea pigs with allergic airway inflammation. In the first phase of our experiment, the animals were sensitized with ovalbumin. Thirty-two sensitized animals were used in two separate experiments according to oxygen concentration breathing: 100 % or 50 % oxygen for 60 h continuously. In each experiment, one group of animals was exposed to hyperoxia, another to ambient air. The cough reflex was induced both by aerosol of citric acid before sensitization, then in sensitized animals at 24 h and 60 h of exposition to oxygen/air in awake animals, and by mechanical stimulation of airway mucosa in anesthetized animals just after the end of the experiment. In contrast to 50 % oxygen, 100 % oxygen breathing leads to significant decrease in chemically induced cough in guinea pigs with allergic inflammation. No significant changes were present in cough induced by mechanical stimulation of airways.

Topics: Animals; Bronchial Hyperreactivity; Citric Acid; Cough; Female; Guinea Pigs; Hyperoxia; Hypersensitivity; Ovalbumin; Oxygen; Reflex; Respiratory Mechanics

To investigate the effect of bradykinin B(2) receptor antagonist FR173657 on cough response in guinea pigs sensitized and challenged with ovalbumin.. 40 normal and 40 sensitized guinea pigs were challenged with the aerosol of ovalbumin. 24 hours later, 10 animals from the normal group and 10 from the sensitized group were intraperitoneally injected either with saline or with 0.03 mg/kg, 0.3 mg/kg and 3 mg/kg of FR173657 respectively, and then cough response to inhaled capsaicin was measured. Specific airway resistance was recorded with a noninvasive technique only in normal, sensitized and FR173657 (0.3 mg/kg)-treated sensitized guinea pigs.. FR173657 did not influence cough response and airway resistance in normal guinea pigs. Compared with normal animals, sensitized guinea pigs presented an increased cough frequency and specific airway resistance [(21.7 +/- 3.0) times/3 min vs (8.3 +/- 1.4) times/3 min, (9.4 +/- 0.5) cm H(2)O/s vs (7.9 +/- 0.9) cm H(2)O/s], (P < 0.05) after inhalation of 10(-4) mol/L capsaicin. The cough frequency and specific airway resistance were decreased to [(12.2 +/- 1.3) times/1 min and (7.5 +/- 0.9) cm H(2)O/s] after administration of 0.3 mg/kg of FR173657 (P < 0.05).. Bradykinin B(2) receptor antagonist inhibited increased cough response and airway resistance in guinea pigs sensitized and challenged with ovalbumin. Bradykinin may be an important mediator in cough associated with eosinophilic airway inflammation.

Topics: Airway Resistance; Animals; Asthma; Bradykinin Receptor Antagonists; Capsaicin; Cough; Disease Models, Animal; Guinea Pigs; Male; Ovalbumin; Quinolines; Receptor, Bradykinin B2

Cough receptor hypersensitivity is a fundamental feature of some conditions presenting with chronic non-productive cough. Suplatast tosilate, an anti-allergic agent, is a T helper (Th)2 cytokine inhibitor that inhibits the synthesis of interleukin (IL)-4, IL-5, immunoglobulin (Ig)E production, and local eosinophil accumulation.. The purpose of this study was to investigate the effect of suplatast on antigen-induced airway cough hypersensitivity and eosinophil infiltration into the airway.. Number of coughs elicited by inhalation of increasing concentrations of capsaicin (10-8, 10-6 and 10-4 M) was counted 24 h after an antigen challenge in conscious guinea-pigs and then bronchoalveolar lavage was performed. We investigated the effect of single (before antigen challenge or capsaicin provocation) or repetitive treatment with intraperitoneal suplatast at a dose of 10 or 30 mg/kg on antigen-induced cough hypersensitivity.. Twenty-four hours after antigen challenge, guinea-pigs developed an increase in cough receptor sensitivity to inhaled capsaicin and eosinophil infiltration in the airways. After a 2-week treatment with suplatast, but not after only a single treatment before antigen challenge or capsaicin provocation, the antigen-induced early phase bronchoconstriction, cough hypersensitivity, and airway eosinophilia were inhibited in a dose-dependent manner.. These results indicate that suplatast inhibits airway cough hypersensitivity underlying allergic eosinophilic inflammation.

Topics: Airway Resistance; Animals; Anti-Allergic Agents; Arylsulfonates; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Bronchoconstriction; Cough; Disease Models, Animal; Eosinophils; Guinea Pigs; Japan; Male; Ovalbumin; Respiratory Hypersensitivity; Sensitivity and Specificity; Sulfonium Compounds; Time Factors

In previous studies, the peptide hormone relaxin (RLX) was found to inhibit mast cell secretion and platelet activation. It has been established that the release of mediators from these cells plays a central pathogenic role in allergic asthma. This prompted us to ascertain whether RLX may counteract the respiratory and histopathological abnormalities of the asthma-like reaction to inhaled antigen in sensitized guinea pigs. Guinea pigs were sensitized with ovalbumin and challenged with the same antigen given by aerosol. Some animals received RLX (30 microg/kg BW, twice daily for 4 days) before antigen challenge. Other animals received inactivated RLX in place of authentic RLX. Respiratory abnormalities, such as cough and dyspnea, were analyzed as were light and electron microscopic features of lung specimens. RLX was shown to reduce the severity of respiratory abnormalities, as well as histological alterations, mast cell degranulation, and leukocyte infiltration in sensitized guinea pigs exposed to ovalbumin aerosol. RLX was also found to promote dilation of alveolar blood capillaries and to reduce the thickness of the air-blood barrier. This study provides evidence for an antiasthmatic property of RLX and raises the possibility of new therapeutic strategies for allergic asthma in humans.

Topics: Administration, Inhalation; Animals; Antigens; Asthma; Bronchi; Cough; Dyspnea; Guinea Pigs; Lung; Male; Ovalbumin; Relaxin; Respiration

The pharmacological mechanisms of allergic cough in the guinea pig were studied. Actively sensitized guinea pigs were exposed to aerosols of antigen to elicit coughing. In separate experiments, naive guinea pigs were exposed to aerosols of capsaicin to elicit coughing. Both allergic and capsaicin-induced cough were inhibited by loratadine (0.3-10 mg kg-1 p.o.) and chlorpheniramine (0.1-3.0 mg kg-1 p.o.). Neither cimetidine (10 mg kg-1 s.c.), nor thioperamide (3-10 mg kg-1 s.c.), inhibited allergic or capsaicin-induced cough. Codeine (3-30 mg kg-1 p.o.), salbutamol (0.003-3.0 mg kg-1 s.c.) and ipratropium (0.03-1.0 mg kg-1 s.c.) inhibited both allergic and capsaicin-induced cough. Hexamethonium (10 and 30 mg kg-1 s.c.) inhibited allergic, but not capsaicin-induced cough. Allergic and capsaicin-induced cough were unaffected by phenidone (5.0 and 10.0 mg kg-1 s.c.). Indomethacin (5.0 and 10.0 mg kg-1 s.c.) had no effect on allergic cough but slightly inhibited capsaicin-induced cough. We conclude that allergic and capsaicin-induced cough are modulated by histamine H1 receptor and cholinergic mechanisms. Histamine H2 or histamine H3 receptor mechanisms, and lipoxygenase and cyclooxygenase products of arachidonic acid metabolism do not influence allergic and capsaicin-induced cough. Ganglionic mechanisms play a minor role in the production of allergic cough and no role in capsaicin-induced cough.

Topics: Administration, Oral; Aerosols; Albuterol; Analysis of Variance; Animals; Antitussive Agents; Capsaicin; Chlorpheniramine; Cimetidine; Codeine; Cough; Drug Hypersensitivity; Guinea Pigs; Hexamethonium; Histamine Antagonists; Indomethacin; Injections, Subcutaneous; Ipratropium; Loratadine; Male; Ovalbumin; Piperidines; Receptors, Histamine H1; Receptors, Histamine H2

The first inhibitor of angiotensin converting enzyme (ACE) was found in and isolated from the venom of the South American pit viper Bothrops jararaca. This was done after it was discovered that bites of the pit viper inhibit the breakdown of a proinflammatory peptide, bradykinin, in prey. Treatment with newly developed orally active ACE-inhibitors has been reported to cause symptoms such as adverse skin reactions, angioneurotic oedema, coughs and, in asthmatics, rapidly decreasing lung function. In this thesis the ACE-inhibitor MK 422 (active parent diacid of enalapril) was demonstrated to potentiate wheal and flare reactions induced by allergens, bradykinin or capsaicin, and to increase infiltration of "inflammatory cells", like eosinophils and neutrophils, into inflammatory dermal test sites in sensitized guinea pigs. MK 422 also augmented spontaneous and allergen-triggered histamine release in vitro from guinea pig skin and lung tissue. Capsaicin "desensitization" of guinea pig skin markedly reduced the wheal and flare reactions to allergens and attenuated the proinflammatory effect of the ACE-inhibitor. The histamine release in vitro from capsaicin-pretreated skin was also decreased, and no clear potentiating effect of MK 422 was demonstrated. In man, enalapril augmented anti-IgE-induced wheal and flare responses and increased bronchial reactivity to histamine. The drop of circulating eosinophils in venous blood was more pronounced after the provocations performed during enalapril treatment, and plasma substance P tended to increase. The alpha 2-adrenoceptor agonist clonidine, known to attenuate "neurogenic inflammation", reduced the wheal and flare reactions in guinea pig skin and decreased infiltration of neutrophils and eosinophils into inflammatory test sites. Furthermore, clonidine abolished the proinflammatory effect of MK 422 on the allergen- evoked wheal and flare reactions in guinea pig skin without counteracting the blood pressure lowering effect of the ACE-inhibitor. Contrarily, an additive hypotensive effect was demonstrated when clonidine was combined with MK 422. It is suggested that the proinflammatory properties demonstrated by ACE-inhibitors is due to augmentation of "neurogenic inflammation".

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Bradykinin; Capsaicin; Cough; Drug Eruptions; Enalapril; Enalaprilat; Guinea Pigs; Histamine Release; Humans; Injections, Intradermal; Ovalbumin; Skin; Skin Tests

Sodium meclofenamate was compared to saline for efficacy in preventing and treating experimentally induced, acute, systemic anaphylaxis in cattle. Respiratroy changes were shown to be reduced to the greatest extent. Lacrimation and collapse were not affected. The timing and routes of administration giving maximum efficacy were those which gave maximum plasma levels of the drug closest to the time of exposure of the animal to the specific antigen.

Topics: Administration, Oral; Anaphylaxis; Animals; Antigens; Cattle; Cattle Diseases; Cough; Injections, Intravenous; ortho-Aminobenzoates; Ovalbumin; Respiratory Insufficiency; Salivation; Toluene