Contraction Of Tracheal Smooth Muscle Research Articles

Vardenafil inhibiting parasympathetic function of tracheal smooth muscle

BackgroundLevitra, a phosphodiesterase-5 (PDE5) inhibitor, is the trade name of vardenafil. Nowadays, it is applied to treatment of erectile dysfunction. PDE5 inhibitors are employed to induce dilatation of the vascular smooth muscle. The effect of Levitra on impotency is well known; however, its effect on the tracheal smooth muscle has rarely been explored. When administered for sexual symptoms via oral intake or inhalation, Levitra might affect the trachea. MethodsThis study assessed the effects of Levitra on isolated rat tracheal smooth muscle by examining its effect on resting tension of tracheal smooth muscle, contraction caused by 10−6 M methacholine as a parasympathetic mimetic, and electrically induced tracheal smooth muscle contractions. ResultsThe results showed that adding methacholine to the incubation medium caused the trachea to contract in a dose-dependent manner. Addition of Levitra at doses of 10−5 M or above elicited a significant relaxation response to 10−6 M methacholine-induced contraction. Levitra could inhibit electrical field stimulation-induced spike contraction. It alone had minimal effect on the basal tension of the trachea as the concentration increased. ConclusionHigh concentrations of Levitra could inhibit parasympathetic function of the trachea. Levitra when administered via oral intake might reduce asthma attacks in impotent patients because it might inhibit parasympathetic function and reduce methacholine-induced contraction of the tracheal smooth muscle.

Th17 cells contribute to pulmonary fibrosis and inflammation during chronic kidney disease progression after acute ischemia.

Acute kidney injury (AKI) is associated with high mortality rates and predisposes development of chronic kidney disease (CKD). Distant organ damage, particularly in the lung, may contribute to mortality in AKI patients. Animal models of AKI demonstrate an increase in pulmonary infiltration of lymphocytes and reveal an acute compromise of lung function, but the chronic effects of AKI on pulmonary inflammation are unknown. We hypothesized that in response to renal ischemia/reperfusion (I/R), there is a persistent systemic increase in Th17 cells with potential effects on pulmonary structure and function. Renal I/R injury was performed on rats, and CKD progression was hastened by unilateral nephrectomy and exposure to 4.0% sodium diet between 35 and 63 days post-I/R. Th17 cells in peripheral blood showed a progressive increase up to 63 days after recovery from I/R injury. Infiltration of leukocytes including Th17 cells was also elevated in bronchiolar lavage (BAL) fluid 7 days after I/R and remained elevated for up to 63 days. Lung histology demonstrated an increase in alveolar cellularity and a significant increase in picrosirius red staining. Suppression of lymphocytes with mycophenolate mofetil (MMF) or an IL-17 antagonist significantly reduced Th17 cell infiltration and fibrosis in lung. In addition, tracheal smooth muscle contraction to acetylcholine was significantly enhanced 63-days after I/R relative to sham-operated controls. These data suggest that AKI is associated with a persistent increase in circulating and lung Th17 cells which may promote pulmonary fibrosis and the potential alteration in airway contractility.

Majie Pingchuan Cataplasm Regulates Thymic Stromal Lymphopoietin in Rats with Asthma

Abstract As a new type of external preparations, cataplasm is widely used in clinical practice. In this study, we aimed to explore the efficacy and mechanism of Majie Pingchuan Cataplasm (MJPC) on asthma. By treating the brown-norway asthmatic rats with MJPC, it was found that the incubation period was significantly longer compared with rats injected with dexamethasone (P<0.05); in addition, the airway smooth muscle spasm was relieved compared with the asthmatic rats (P<0.05); it was observed that the number of inflammatory cells (such as eosinophils and neutrophils) was reduced both in the blood and lung tissue (P<0.05). The efficacy of MJPC was also explored in vitro. Components of MJPC had an antagonistic effect on the tracheal smooth muscle contraction of guinea pigs induced with histamine phosphate and acetylcholine chloride. It has been proven that thymic stromal lymphopoietin (TSLP) plays an important role in the pathogenesis of atopic dermatitis and asthma. So we hypothesized that TSLP may be an important regulator of immune system in the skin and lung. In this study, TSLP levels in different tissues were detected to explore the mechanism of MJPC in the treatment of asthma. The results showed that expressions of TSLP in the lung tissue, skin, bronchoalveolar lavage fluid and serum were significant lower in the MJPC group compared with the model group (P<0.05). Our study confirmed that MJPC has a therapeutic effect on asthma in rats, it can not only play a role in blood after percutaneous absorption, but also regulate the skin immune system to achieve the treatment of asthma by affecting the expression of TSLP in local skin.

各種揮発性麻酔薬の吸入は頚部迷走神経刺激およびアセチルコリンによるイヌ気管平滑筋収縮を抑制する : In vivoイヌ等尺性気管平滑筋張力測定による検討

各種揮発性麻酔薬の吸入は頚部迷走神経刺激およびアセチルコリンによるイヌ気管平滑筋収縮を抑制する : In vivoイヌ等尺性気管平滑筋張力測定による検討

Effects of magnesium sulfate on airway smooth muscle contraction in rats.

Aim To investigate the effect of magnesium sulfate (MgSO4) at different doses on isolated tracheal smooth muscle contraction in rats induced by different mechanisms. Methods Twelve rats' tracheas were placed into organ bath. Consecutively, acetylcholine (10-6,10-5,10-4 M), histamine(10-8,10-5,10-3 M) and KCl (30,60 mM) solutions was administered for contractions. MgSO4 from 10-4 to 10-1 M concentrations were subsequently administered after each constrictive agent and relaxation degrees were recorded. Results In the acetylcholine and KCl groups, dose dependent strong contractions were observed, but not in the histamine group and that group was excluded. Significant relaxation occurred with gradually increasing doses of MgSO4. In the high dose KCl group, a slight increase in contractions after the administration of 10-4 and 10-3 M MgSO4 was recorded. Conclusion We suggest that MgSO4 is effective in relaxing airway smooth muscle contractions caused by different factors; however, it must be considered that low doses of MgSO4 may only lead to a slight increase in contractions.

Bronchodilatory, antitussive and anti-inflammatory effect of morin in the setting of experimentally induced allergic asthma.

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.

Menthol inhibiting parasympathetic function of tracheal smooth muscle.

Menthol is used as a constituent of food and drink, tobacco and cosmetics nowadays. This cold receptor agonist has been used as a nasal inhalation solution in the daily life. The effect of menthol on nasal mucosa in vivo is well known; however, the effect of the drug on tracheal smooth muscle has been rarely explored. Therefore, during administration of the drug for nasal symptoms, it might also affect the trachea via oral intake or inhalation. We used our preparation to test the effectiveness of menthol on isolated rat tracheal smooth muscle. A 5 mm long portion of rat trachea was submersed in 30 ml Krebs solution in a muscle bath at 37ºC. Changes in tracheal contractility in response to the application of a parasympathetic mimetic agent were measured using a transducer connected to a Pentium III computer equipped with polygraph software. The following assessments of menthol were performed: (1) effect on tracheal smooth muscle resting tension; (2) effect on contraction caused by 10-6 M methacholine as a parasympathetic mimetic; (3) effect of the drug on electrically induced tracheal smooth muscle contractions. Results indicated that addition of a parasympathetic mimetic to the incubation medium caused the trachea to contract in a dose-dependent manner. Addition of menthol at doses of 10-5 M or above elicited a relaxation response to 10-6 M methacholine-induced contraction. Menthol could also inhibit electrical field stimulation (EFS) induced spike contraction. However, it alone had a minimal effect on the basal tension of trachea as the concentration increased. We concluded that the degree of drug-induced tracheal contraction or relaxation was dose-dependent. In addition, this study indicated that high concentrations of menthol might actually inhibit parasympathetic function of the trachea.

Effects of levobupivacaine on isolated rat tracheal smooth muscle

Levobupivacaine has been developed as a safer alternative to bupivacaine because of its reduced systemic toxicity. However, the effect of directly delivering levobupivacaine into tracheal smooth muscle has not been adequately explored. We performed this study to determine the in vitro effects of levobupivacaine on isolated rat tracheal smooth muscle. A portion of rat trachea 5 mm in length was mounted in 30 ml of Krebs solution in a muscle bath at 37 °C. The following effects of levobupivacaine were assessed: (1) the effect on tracheal smooth muscle resting tension (n = 6), (2) the effect on contraction caused by 10(-6) M methacholine (n = 6) and (3) the effect on electrically induced tracheal smooth muscle contractions (n = 6). Levobupivacaine caused dose-dependent relaxation in the trachealis muscle precontracted with 10(-6) M methacholine. Contraction inhibition was statistically significant when 10(-5) and 10(-4) M levobupivacaine were applied, compared with the contraction inhibition that occurred in the control groups (p < 0.01). A high dose of levobupivacaine also decreased the spike contraction induced by electrical field stimulation. This study indicated that high concentrations of levobupivacaine might antagonize the cholinergic receptors and inhibit parasympathetic function of the trachea.

Preliminary Investigations of the Anti-asthmatic Properties of the Aqueous Extract of Justicia pectoralis (Fresh Cut).

Justicia pectoralis (fresh cut plant), family Acantheceae, is a herb that is native to central America and the Caribbean. A crude extract prepared from the leaves of Justicia pectoralis is commonly used in Jamaican ethnotraditional medicine to reduce difficulty in breathing and suppress wheezing in asthmatic individuals. To investigate the anti-inflammatory and antihistamine activity of an aqueous extract of Justicia pectoralis. In in vivo experiments, guinea pigs were sensitized by the method of Weinrich and Undem (1987). The effect of water on the wheals was assessed in the control group, n = 4. The effect of 3.3 mg of the crude extract was noted in histamine-induced wheals over a period of three hours. The extract was injected via intraperitoneal injections. In in vitro experiments, 3.3 mg of crude sample was tested for its effectiveness against histamine-induced tracheal contraction caused by cumulative dosing of histamine. The crude extract was efficacious in reducing the formation of histamine-induced wheals (p < 0.05). Results obtained from in vitro studies indicated that the crude extract (3.3 mg) caused significant reduction in tracheal smooth muscle contraction resulting from cumulative doses of histamine (p < 0.05). However, as the histamine doses increased, fresh cut extract was not able to maintain inhibition of histamine-induced tracheal smooth muscle contraction. This is an indication that the extract showed competitive reversible antagonism, possibly at histamine receptors. A crude extract of the leaves Justicia pectoralis reduced the formation of histamine-induced wheals in sensitized guinea pigs (p < 0.05) and also reduced histamine-induced tracheal smooth muscle contractions (p < 0.05). It blocked the effect of contraction produced by histamine in the airways; this property supports folklore claims for its use as an antihistamine.

Comparative Study of Protective Effects of Salbutamol and Beclomethasone against Insulin Induced Airway Hyper-reactivity on Isolated Tracheal Smooth Muscle of Guinea Pig.

Inhalational insulin was withdrawn from the market due to its potential to produce airway hyper-reactivity and bronchoconstriction. So the present study was designed to explore the acute effects of insulin on airway reactivity of guinea pigs and protective effects of salbutamol and beclomethasone against insulin induced airway hyper-responsiveness on isolated tracheal smooth muscle of guinea pig. Effects of varying concentrations of insulin (10(-7) to 10(-3) M), insulin pretreated with fixed concentration of salbutamol (10(-7) M) and beclomethasone (10(-6) M) were studied on isolated tracheal tissue of guinea pig by constructing cumulative concentration response curves. Changes in tracheal smooth muscle contractions were recorded on four channel oscillograph. The mean ± SEM of maximum amplitudes of contraction with increasing concentrations of insulin, insulin pretreated with fixed concentration of salbutamol and beclomethasone were 35 ± 1.13 mm, 14.55 ± 0.62 mm and 22 ± 1.154 mm respectively. Although salbutamol and beclomethasone both had a profound inhibitory effect on insulin induced airway hyper-reactivity, yet salbutamol is more efficacious than beclomethasone. So we suggest that pretreatment of inhaled insulin with salbutamol may be preferred over beclomethasone in amelioration of its potential respiratory adverse effects such as bronchoconstriction.

Benzydamine oral spray inhibiting parasympathetic function of tracheal smooth muscle.

ObjectivesBenzydamine is a nonsteroidal anti-inflammatory agents agent with anti-inflammatory and local anesthesia properties that is available in the entire world as an oral spray for oral mucositis patients who are suffering from radiation effects. The effect of benzydamine on oral mucositis in vivo is well known; however, the effect of the drug on tracheal smooth muscle has rarely been explored. During administration of the benzydamine for oral symptoms, it might affect the trachea via oral intake or inhalation.MethodsWe examined the effectiveness of benzydamine on isolated rat tracheal smooth muscle. The following assessments of benzydamine were performed: effect on tracheal smooth muscle resting tension; effect on contraction caused by 10-6M methacholine as a parasympathetic mimetic; and effect of the drug on electrically induced tracheal smooth muscle contractions.ResultsAddition of methacholine to the incubation medium caused the trachea to contract in a dose-dependent manner. Addition of benzydamine at doses of 10-5M or above elicited a significant relaxation response to 10-6M methacholine-induced contraction. Benzydamine could inhibit electrical field stimulation-induced spike contraction. It alone had a minimal effect on the basal tension of trachea as the concentration increased.ConclusionThis study indicated that high concentrations of benzydamine might actually inhibit parasympathetic function of the trachea. Benzydamine might reduce asthma attacks in oral mucositis patients because it could inhibit parasympathetic function and reduce methacholine-induced contraction of tracheal smooth muscle.

Effect of kidsolone on isolated rat′s tracheal smooth muscle

Purpose: Prednisolone (Kidsolone) is an anti-inflammatory drug that is mainly used for patients with chronic obstructive airway diseases (COAD), such as asthma and chronic obstructive pulmonary diseases (COPD). The objective of this study was to determine the effects of Kidsolone on the trachea of rats in vitro . Materials and Methods: We tested the effectiveness of Kidsolone on isolated rat trachea submersed in Krebs solution in a muscle bath. Changes in tracheal contractility in response to the application of parasympathetic mimetic agents were measured. The following assessments of Kidsolone were performed: (1) Effect on tracheal smooth muscle resting tension; (2) effect on contraction caused by 10-6 M methacholine; (3) effect of the drug on electrically-induced tracheal smooth muscle contractions. Result: Our results demonstrated that no significant effects were induced by the addition of 10-8-10-5 M Kidsolone on tracheal tension after methacholine treatment, indicating that Kidsolone had no anti-cholinergic effect. It alone had a minimal effect on the basal tension of the trachea as the concentration increased. Furthermore, Kidsolone did not affect electrical field stimulation-induced spike contraction, which represent the Kidsolone could not antagonize the parasympathetic innervation responsible for trachea smooth muscle contraction. Conclusion: The immediate effect of Kidsolone on COAD may be indirectly. Therefore, sorely use of inhalation Kidsolone without β2-agonist in treating acute asthma or COPD attack may be more suboptimal than co-administration of them.

Effects of sumatriptan nasal spray (Imigran) on isolated rat's tracheal smooth muscle.

Sumatriptan (Imigran) is a potent and highly selective 5-HT1 receptor agonist often used in treating acute migraine. Intranasal sumatriptan is well absorbed and is generally effective in relieving headache. However, the effects of Imigran given intratracheally have rarely been well explored. We aimed to verify the effect of Imigran, which acts on the tracheal smooth muscle directly in vitro. We examined the effectiveness of Imigran on isolated rat tracheal smooth muscle by testing: (1) effect on tracheal smooth muscle resting tension; (2) effect on contraction caused by 10(-6) M methacholine as a parasympathetic mimetic; (3) effect of the drugs on electrically induced tracheal smooth muscle contractions. The results indicated that the addition of methacholine to the incubation medium caused the trachea to contract in a dose-dependent manner. The addition of Imigran at doses of 10(-5) M or above elicited a significant relaxation response to 10(-6) M methacholine-induced contraction. Imigran could inhibit electrical field stimulation-induced spike contraction. It also had a minimal effect on the basal tension of trachea as the concentration increased. The study indicated high concentrations of Imigran could cause bronchodilation to reduce asthma attacks not only by blocking parasympathetic tone, but also by directly antagonizing the effect of cholinergic receptors.

A Comparative Study of the Beneficial Effects of Ipratropium and Beclomethasone against Insulin-Induced Tracheal Tissue Contraction in a Guinea Pig Model

Objective: To evaluate the acute effects of insulin on airway reactivity and the protective effects of beclomethasone and ipratropium against insulin-induced airway hyperresponsiveness on isolated tracheal smooth muscle in a guinea pig model. Materials and Methods: The trachea of each guinea pig was excised; one end of the tracheal strip was attached to the hook of the oxygen tube of a tissue bath and the other end was connected to a research-grade isometric force displacement transducer. The effects of varying concentrations of insulin (10^-7 to 10^-3<smlcap>M</smlcap>) and insulin pretreated with a fixed concentration of beclomethasone (10^-6<smlcap>M</smlcap>) and ipratropium (10^-6<smlcap>M</smlcap>) on the isolated tracheal tissue were studied by constructing cumulative concentration-response curves. Changes in tracheal smooth muscle contractions were recorded on a 4-channel oscillograph. Results: The means ± standard error of the mean of the maximum amplitude of contraction with increasing concentrations of insulin and of insulin pretreated with fixed concentrations of beclomethasone and ipratropium were 35 ± 1.13, 22 ± 1.15 and 27.8 ± 1.27 mm, respectively. Conclusion: The data showed that beclomethasone inhibited the contractile response of insulin to a greater extent than ipratropium. Thus we suggest that inhalational insulin pretreated with beclomethasone may be more efficacious than with ipratropium for the amelioration of potential respiratory adverse effects such as bronchoconstriction.

Steroids and antihistamines synergize to inhibit rat's airway smooth muscle contractility.

Both glucocorticoids and H1-antihistamines were widely used on patients with allergic rhinitis (AR) and obstructive airway diseases. However, their direct effects on airway smooth muscle were not fully explored. In this study, we tested the effectiveness of prednisolone (Kidsolone) and levocetirizine (Xyzal) on isolated rat trachea submersed in Kreb's solution in a muscle bath. Changes in tracheal contractility in response to the application of parasympathetic mimetic agents were measured. The following assessments of the drug were performed: (1) effect on tracheal smooth muscle resting tension; (2) effect on contraction caused by 10(-6) M methacholine; (3) effect of the drug on electrical field stimulation (EFS) induced tracheal smooth muscle contractions. The result revealed sole use of Kidsolone or Xyzal elicited no significant effect or only a little relaxation response on tracheal tension after methacholine treatment. The tension was 90.5 ± 7.5 and 99.5 ± 0.8 % at 10(-4) M for Xyzal and 10(-5) M for Kidsolone, respectively. However, a dramatically spasmolytic effect was observed after co-administration of Kidsolone and Xyzal and the tension dropped to 67.5 ± 13.6 %, with statistical significance (p < 0.05). As for EFS-induced contractions, Kidsolone had no direct effect but Xyzal could inhibit it, with increasing basal tension. In conclusion, using glucocorticoids alone had no spasmolytic effect but they can be synergized with antihistamines to dramatically relax the trachea smooth muscle within minutes. Therefore, for AR patients with acute asthma attack, combined use of those two drugs is recommended.

Preventive effects of ipratropium and salbutamol against insulin induced tracheal smooth muscle contraction in guinea pig model

Inhalational insulin was withdrawn from the market due to its potential to produce airway hyper-reactivity and bronchoconstriction. So the present study was designed to explore the acute effects of insulin on airway reactivity of guinea pigs and protective effects of salbutamol and ipratropium against insulin induced airway hyper-responsiveness on isolated tracheal smooth muscle of guinea pig. The tracheal muscle contractions were recorded with transducer on four channel oscillograph. The mean ± SEM of maximum amplitude of contraction with increasing concentrations of insulin (10-7- 10-3 M ), insulin pretreated with fixed concentration of salbutamol (10-7 M) and ipratropium (10-6 M) were 35 ± 1.13 mm, 14.55 ± 0.62 mm and 27.8 ± 1.27 mm respectively. Salbutamol inhibited the contractile response of insulin greater than ipratropium on isolated tracheal muscle of guinea pig. So we suggest that pretreatment of inhaled insulin with salbutamol may be preferred over ipratropium in amelioration of its potential respiratory adverse effects such as bronchoconstriction.

Insulin causes airway hyper-reactivity

Background: We explored the acute effects of insulin and one possible mechanism underlying the acute contractile effects of insulin on isolated tracheal smooth muscle of guinea pig in vitro. Methods: Effects of increasing concentrations of histamine (10 −7 -10 −3 M), insulin (10 −7 -10 −3 M), insulin pretreated with a fixed concentration of indomethacin (10 −6 M) were studied on isolated tracheal tissue of guinea pig in vitro by constructing cumulative concentration response curves. The tracheal smooth muscle contractions were recorded with transducer on four channel oscillograph. Results: Histamine and insulin produced a concentration-dependent reversible contraction of isolated tracheal muscle of guinea pig. The mean±standard error of the mean of maximum amplitudes of contraction with histamine, insulin and insulin pretreated with indomethacin were 92.5±1.20 mm, 35±1.13 mm and 14.55±0.62 mm respectively. Indomethacin shifted the concentration-response curve of insulin to the right and downwards. Conclusions: Insulin has acute contractile effects on guinea pig airways, which were significantly inhibited by prostaglandin synthesis inhibitor indomethacin confirming the involvement of contractile prostaglandins in insulin-induced airway hyper-responsiveness.

Efficacy of fexofenadine in isolated rat tracheas

Objectives: Histamine is an important chemical mediator in both nasal and bronchial inflammation in patients with allergic rhinitis and asthma. The effect of histamine receptor-1 antagonists on nasal mucosa in vivo is well known, however, the effect on tracheal smooth muscle has rarely been explored. The purpose of this study was to determine the effects of fexofenadine on isolated tracheal smooth muscle in vitro. Methods: Six tracheal strips were used for each experiment, and one untreated strip served as a control. We examined the effectiveness of fexofenadine on isolated rat tracheal smooth muscle by testing the effect on: 1) tracheal smooth muscle resting tension; 2) contraction caused by 10E-6 M methacholine as a parasympathetic mimetic; and 3) electrically induced tracheal smooth muscle contractions. Results: The results indicated that addition of methacholine caused the trachea to contract in a dose-dependent manner. The addition of fexofenadine at a dose of 10E-4 M elicited a significant relaxation response compared to 10E-6 M methacholine-induced contraction. There were no detectable changes in the peak tension of electrical field stimulation-induced contractions in the fexofenadine group. Conclusion: High concentrations of fexofenadine had an anti-cholinergic effect. In addition to diminishing histamine-mediated allergic symptoms, fexofenadine may have a potentially therapeutic implication in alleviating asthma-related symptoms due to reducing methacholine-induced contractions of tracheal smooth muscle though these aspects were not studied.

Effects of inhaled aminophylline on airway constriction and inflammation in ovalbumin-sensitized guinea pigs

Background: The systemic administration of theophylline is useful for asthma treatment. However its narrow therapeutic range makes it difficult to use. Little is known about its potential in inhalation therapy, particularly repeated inhalation.Objective: The purpose of this study is to investigate the therapeutic usefulness of inhaled aminophylline in an asthma model.Methods: The effects of pretreatment with inhaled aminophylline (25 mg/mL for 30 min/dose) on airway response and inflammation after an ovalbumin (OVA) challenge and airway hypersensitivity to acetylcholine (Ach) were evaluated using guinea pigs sensitized with OVA.Results: Aminophylline relaxed the ACh-induced contraction of tracheal smooth muscle in vitro in a concentration-dependent manner. Pretreatment with single-dose aminophylline inhalation suppressed OVA-induced airway constriction to the same extent as the intraperitoneal pretreatment with high-dose aminophylline (10–20 mg/kg). However, pretreatment with single-dose aminophylline inhalation did not suppress eosinophil infiltration into airways (neither bronchoalveolar lavage [BAL] fluid nor lung tissue) and did not suppress airway hyperreactivity to ACh, 24 h after OVA challenge. Repeated inhalation of aminophylline (twice daily for 7 days) suppressed the infiltration of eosinophils and suppressed airway hypersensitivity to ACh. In addition, high concentrations of aminophylline inhibited production of oxygen radicals by BAL cells.Conclusion: Single-dose inhalation treatment with aminophylline has transient but relatively strong bronchodilating effects due to delivery of high doses into local airways. Repeated inhalation treatment suppressed airway inflammation and hypersensitivity induced by allergens. Therefore, inhaled aminophylline may be useful for asthma treatment.

Effects of Dexmedetomidine on the Isolated Rat Tracheal Smooth Muscle

Background/Purpose Intranasally administered dexmedetomidine, a highly selective α2-adrenoceptor agonist, has been found to an effective premedication in children. However, the effect of delivering dexmedetomidine directly into the tracheal smooth muscle through inhalation has not been adequately explored. The objective of this study was to determine the effects of dexmedetomidine on the isolated rat tracheal smooth muscle in vitro. Methods A portion of rat trachea (5 mm in length) was mounted in a muscle bath filled with 30 mL of Krebs solution at 37°C. The following effects of dexmedetomidine were assessed: (1) effect on the tracheal smooth muscle resting tension, (2) effect on contraction caused by 10−6 M methacholine, and (3) effect on electrically induced tracheal smooth muscle contractions. Results Dexmedetomidine elicited a negligible effect on the basal tension of the trachea as its concentration was increased. Dexmedetomidine caused a concentration-dependent relaxation in the trachealis muscle precontracted with 10−6 M methacholine, but did not affect the contractile response to electrical field stimulation. Conclusion The results of this study suggest that high concentrations of dexmedetomidine might have an antispasmodic effect on the tracheal smooth muscle.