吸入过硫酸铵抑制豚鼠离体气管中非肾上腺素能、非胆碱能舒张。

Inhaled ammonium persulphate inhibits non-adrenergic, non-cholinergic relaxations in the guinea pig isolated trachea.

机构信息

Department of Preventive, Occupational and Community Medicine, University of Pavia, Pavia, Italy. antonio.dellabianca @ unipv.it

出版信息

Respiration. 2010;79(5):411-9. doi: 10.1159/000259041. Epub 2009 Nov 18.

DOI:10.1159/000259041

PMID:19923787

Abstract

BACKGROUND

Persulphates can act both as irritants and sensitizers in inducing occupational asthma. A dysfunction of nervous control regulating the airway tone has been hypothesized as a mechanism underlying bronchoconstriction in asthma.

OBJECTIVES

It was the aim of this study to investigate whether inhaled ammonium persulphate affects the non-adrenergic, non-cholinergic (NANC) inhibitory innervation, the cholinergic nerve-mediated contraction or the muscular response to the spasmogens, carbachol or histamine, in the guinea pig epithelium-free, isolated trachea.

METHODS

Male guinea pigs inhaled aerosols containing ammonium persulphate (10 mg/m(3) for 30 min for 5 days during 3 weeks). Control animals inhaled saline aerosol. NANC relaxations to electrical field stimulation at 3 Hz were evaluated in whole tracheal segments as intraluminal pressure changes. Drugs inactivating peptide transmission, nitric oxide synthase, carbon monoxide production by haem oxygenase-2 and soluble guanylyl cyclase were used to assess the involvement of various inhibitory neurotransmitters. Carbachol and histamine cumulative concentration-response curves were obtained.

RESULTS

In both groups, nitric oxide and carbon monoxide participated to the same extent as inhibitory neurotransmitters. In exposed animals, the tracheal NANC relaxations were reduced to 45.9 +/- 12.1% (p < 0.01). The cholinergic nerve-mediated contractions to electrical field stimulation and the muscular response to histamine were not modified by ammonium persulphate exposure. The muscular response to carbachol was unaffected up to 1 microM. Conversely, the response to the maximal concentration of carbachol (3 microM) was increased (p < 0.01).

CONCLUSION

Ammonium persulphate inhalation at high concentrations impairs the nervous NANC inhibitory control in the guinea pig airways. This may represent a novel mechanism contributing to persulphate-induced asthma.

摘要

背景

过硫酸盐既能作为刺激物，也能作为敏化剂，诱发职业性哮喘。气道张力的神经控制功能障碍被认为是哮喘导致支气管收缩的一种机制。

目的

本研究旨在探讨吸入过硫酸铵是否会影响豚鼠去上皮、分离气管中非肾上腺素能、非胆碱能（NANC）抑制性神经支配、胆碱能神经介导的收缩或对痉挛剂乙酰甲胆碱或组胺的肌肉反应。

方法

雄性豚鼠吸入过硫酸铵气溶胶（3 周内，5 天，每天 30 分钟，浓度为 10 mg/m3）。对照组动物吸入生理盐水气溶胶。通过腔内压力变化评估 3 Hz 电刺激引起的全气管段 NANC 松弛。使用失活肽传递、一氧化氮合酶、血红素加氧酶-2 产生的一氧化碳和可溶性鸟苷酸环化酶的药物来评估各种抑制性神经递质的参与。获得乙酰甲胆碱和组胺的累积浓度-反应曲线。

结果

在两组中，一氧化氮和一氧化碳都作为抑制性神经递质起到了相同的作用。在暴露组动物中，气管 NANC 松弛作用降低至 45.9±12.1%（p<0.01）。电刺激引起的胆碱能神经介导的收缩和对组胺的肌肉反应不受过硫酸铵暴露的影响。乙酰甲胆碱的肌肉反应在 1 μM 时不受影响。相反，对乙酰甲胆碱的最大浓度（3 μM）的反应增加（p<0.01）。