Tokunao Amemiya

Involvement of NK2 receptors rather than NK1 receptors in bronchial hyperresponsiveness induced by allergic reaction in guinea‐pigs

1 In this study, the role of neuropeptides in antigen‐induced bronchoconstriction and bronchial responsiveness in guinea‐pigs was evaluated by use of phosphoramidon, the inhibitor of neutral endopeptidases (NEP), the NK1 receptor antagonist, FK888, and the dual NK1/NK2 receptor antagonist, FK224. The role of endogenous tachykinins in bronchial hyperresponsiveness induced by inhaled capsaicin was also observed with FK888 and FK224. 2 Allergic bronchoconstriction and bronchial responsiveness was evoked by inhalation of ovalbumin (OA), and increasing doses of methacholine were inhaled at 5‐min intervals for 30 min after OA challenge in passively sensitized and artificially ventilated guinea‐pigs. Animals were treated with a 30 s inhalation of phosphoramidon (10−3m) or saline 10 min before the OA challenge. FK888 (1.0 or 10 mg kg−1) or FK224 (1.0 or 10 mg kg−1) was administered intravenously 5 min before the OA challenge. 3 Treatment with phosphoramidon did not alter the increase in the lateral pressure at the tracheal tube (Pao) caused by OA inhalation or the increase in bronchial response to methacholine following the allergic reaction. Pretreatment with FK224 did not inhibit the increase in Pao after antigen provocation but did significantly inhibit antigen‐induced bronchial hyperresponsiveness in a dose‐dependent manner, while FK888 did not affect either allergic bronchoconstriction or post‐allergic bronchial hyperresponsiveness. 4 Histamine, 25, 50, 100 or 200 μ ml−1 was inhaled for 20 s at 5‐min intervals in non‐sensitized guinea‐pigs which were pretreated with inhalation of subthreshold dose of capsaicin (10−7 m). FK888 or FK224, each at a dose of 0.1 or 1.0 mg kg−1, or vehicle was given to guinea‐pigs intravenously 3 min before inhalation of capsaicin. The capsaicin inhalation significantly potentiated bronchial responsiveness to histamine, compared with control. The capsaicin‐induced bronchial hyperresponsiveness was completely blocked by FK224 in a dose‐dependent manner but not by FK888. 5 These results suggest that NK2 receptors rather than NK1 receptors may play an important role in bronchial hyperresponsiveness induced by antigen challenge as well as capsaicin while tachykinins do not play a primary role in the acute bronchospasm elicited by antigen challenge in passively sensitized guinea‐pigs.

A partial involvement of histamine in ultrasonically nebulized distilled water-induced bronchoconstriction in guinea-pigs

1 Inhalation of ultrasonically nebulized distilled water (UNDW) can induce bronchoconstriction only in asthmatics, but mechanisms of the response are not well known. We recently reported a guinea‐pig model of UNDW‐induced bronchoconstriction (UNDW‐IB) in which UNDW induces bronchoconstriction when UNDW is inhaled 20 min after a challenge with aerosolized ovalbumin (OA) in passively sensitized, anaesthetized and artificially ventilated guinea‐pigs. 2 To elucidate the role of histamine in the UNDW‐IB, we examined the effects of antihistamines, diphenhydramine hydrochloride (DH) and chlorpheniramine maleate (CP), and measured histamine content in bronchoalveolar lavage fluid (BALF) in the animal model. 3 DH in doses of 0.1, 1.0 and 10 mg kg−1 and CP in doses of 0.01, 0.1 and 1.0 mg kg−1 administered intravenously 15 min after the OA challenge partially reduced the UNDW‐IB at 1 and 2 min after the UNDW inhalation in a dose‐dependent manner. Histamine content in BALF recovered 10 min after the UNDW inhalation following the OA provocation was significantly increased compared with that after saline inhalation and before the UNDW inhalation following the OA challenge. 4 Intravenous atropine in a dose of 0.5 mg kg−1 or inhaled disodium cromoglycate in concentrations of 1 and 10 mg ml−1 did not alter the UNDW‐IB. 5 These results suggest that histamine is involved in part in the UNDW‐IB in our animal model.

In vivo airway eosinophil accumulation induced by polymyxin‐B reduces bronchial responsiveness in guinea pigs

Background Chronic desquamative eosinophilic bronchitis and bronchial hyperresponsiveness have been considered essential for bronchial asthma. However, it has not been studied whether airway eosinophils enhance or inhibit bronchial responsiveness in vivo.

Necrotizing Bronchial Aspergillosis as a Cause of Hemoptysis in Sarcoidosis

The case history is presented of a patient with recurrent massive hemoptysis caused by necrotizing bronchial aspergillosis associated with sarcoidosis. The involved segments (right IX and X) were resected for treatment of the life-threatening hemoptysis. Histologic examination of the resected specimen confirmed the diagnosis. Necrotizing bronchial aspergillosis is a rare variant form of invasive pulmonary aspergillosis and has not been described previously as a cause of hemoptysis in sarcoidosis.

Peptide leukotrienes mediate acetaldehyde-induced bronchial hyper-responsiveness in guinea-pigs

Background We previously reported that inhaled acetaldehyde, a metabolite of ethanol atid a maiti factor in alcohol‐induced asthma, causes bronchial hyper‐responsiveness (BHR) in asthmatics. However, the mechanisms are unclear.

Lack of adrenomedullin on antigen-induced bronchoconstriction in guinea pigs in vivo

Antigen challenge can provoke acute bronchoconstriction, recognized as immediate asthmatic response (IAR), but the evolving events in this reaction are not well defined. Recently, a novel peptide, designated adrenomedullin, was isolated from human pheochromocytoma, and has been shown to have potent systemic and pulmonary vasodilator activity.The purpose of this study was to elucidate the influence of adrenomedullin in the development of IAR. Passively sensitized guinea pigs were anesthetized and treated with diphenhydramine hydrochloride, and then artificially ventilated. Ovalbumin was inhaled after an intravenous administration of adrenomedullin. Other studies were performed in naive guinea pigs to investigate the airway responses to inhaled methacholine or histamine after an intravenous administration of adrenomedullin. Antigen challenge caused bronchoconstriction in sensitized guinea pigs. Adrenomedullin did not inhibit the antigen-induced bronchoconstriction in sensitized guinea pigs or the dose-dependent responses to inhaled methacholine or histamine in naive animals in spite of its vasodilating effect. We conclude that an intravenous administration of adrenomedullin does not influence antigen-induced bronchoconstriction or bronchial responsiveness to inhaled methacholine or histamine in vivo.

No involvement of lipid mediators in a guinea pig model of ultrasonically nebulized distilled water-induced bronchoconstriction.

An inhalation of ultrasonically nebulized distilled water (UNDW) induces bronchoconstriction only in asthmatics, but the mechanism underlying the response is not fully understood. We have reported that bronchoconstriction occurs immediately after UNDW is inhaled 20 min after an antigen challenge in guinea pigs. Our aim was to examine the role of lipid mediators in this response. Passively sensitized guinea pigs were anesthetized and artificially ventilated. A sulfidopeptide leukotriene receptor antagonist, KCA-757, and platelet-activating factor antagonists, Y-24180 and E6123, were administered i.v. 15 min after an aerosolized antigen challenge, and UNDW was inhaled 5 min later. KCA-757, Y-24180, or E6123 did not, significantly alter the UNDW-induced bronchoconstriction. Together with our previous data that thromboxane A2 receptor antagonists did not influence the UNDW-induced bronchoconstriction, the present results suggest that lipid mediators are not involved in the UNDW-induced bronchoconstriction in our guinea pig model.

In vivo airway eosinophil accumulation does not enhance antigen- or propranolol-induced bronchoconstriction in guinea pigs

BACKGROUND Chronic airway eosinophil accumulation is characteristic of asthma. However, it remains unclear whether airway eosinophils enhance or reduce release of chemical mediators and/or action of the released mediators in the airways in vivo, because previous investigators have indicated that eosinophil-derived factors such as histaminase and arylsulfatase may alter the allergic reaction by metabolizing chemical mediators. Recently, we have developed a guinea pig model of propranolol-induced bronchoconstriction (PIB), which is mediated by lipid mediators such as thromboxane A2 (TxA2), cysteinyl leukotrienes (cLTs) and platelet activation factor (PAF). This study was conducted to explain the influence of airway eosinophil accumulation on antigen-induced bronchoconstriction and the following PIB, both of which are mediated by lipid mediators. METHODS Guinea pigs were transnasally treated with 75 microg/kg of polymyxin-B or vehicle twice a week for a total of 3 weeks. Guinea pigs were anesthetized and treated with diphenhydramine hydrochloride, and then artificially ventilated 24 h after the last administration of polymyxin-B or vehicle followed by passive sensitization. Propranolol at a concentration of 10 mg/ml was inhaled 20 min after an aerosolized antigen challenge. RESULTS The proportion of eosinophils in bronchoalveolar lavage fluid obtained 15 min after the propranolol inhalation was significantly increased in guinea pigs treated with polymyxin-B compared with the vehicle. The polymyxin-B treatment did not affect antigen-induced bronchoconstriction or the following PIB. CONCLUSIONS We conclude that eosinophils accumulated in the airways by polymyxin-B does not affect release of chemical mediators induced by antigen or propranolol inhalation, or action of released mediators in vivo.