In vitro tracheal hyperresponsiveness to muscarinic receptor stimulation by carbachol in a rat model of bleomycin-induced pulmonary fibrosis

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RESEARCH PRODUCT

In vitro tracheal hyperresponsiveness to muscarinic receptor stimulation by carbachol in a rat model of bleomycin-induced pulmonary fibrosis

Ricardo Guijarro Julio Cortijo Julio Cortijo Manuel De La Mata P. Blasco Javier Milara J. Barrio Esteban J. Morcillo

subject

Male medicine.medical_specialty Carbachol Pulmonary Fibrosis Stimulation In Vitro Techniques Muscarinic Agonists Lung injury Calcium in biology Proinflammatory cytokine Rats Sprague-Dawley Bleomycin Fibrosis Internal medicine Pulmonary fibrosis Muscarinic acetylcholine receptor medicine Animals Calcium Signaling Pharmacology Dose-Response Relationship Drug Tumor Necrosis Factor-alpha business.industry Muscle Smooth respiratory system medicine.disease Receptors Muscarinic Rats Trachea Disease Models Animal Endocrinology Carbachol Bronchial Hyperreactivity business Interleukin-1 Muscle Contraction medicine.drug

description

Summary 1 Bleomycin-induced lung injury is widely used as an experimental model to investigate the pathophysiology of pulmonary fibrosis but the alterations in the pharmacological responsiveness of airways isolated from bleomycin-exposed animals has been scarcely investigated. The aim of this study was to examine the in vitro tracheal responses to muscarinic receptor stimulation with carbachol in a rat bleomycin model. 2 Concentration–response curves to carbachol (10 nm to 0.1 mm) were obtained in tracheal rings isolated from Sprague–Dawley rats 14 days after endotracheal bleomycin or saline. The intracellular calcium signal in response to carbachol (10 μm) was measured by epifluorescence microscopy using fura-2 in primary cultures of tracheal smooth muscle cells from bleomycin- and saline-exposed rats. Circulating plasma tumour necrosis factor (TNF)-α/interleukin (IL)-1β levels were measured by enzyme-linked immunosorbent assay. 3 Maximal contraction in response to carbachol was significantly greater in tracheal rings from bleomycin-exposed rats compared with controls (15.8 ± 1.3 mN vs. 11.8 ± 1.4 mN; n = 19, P < 0.05). 4 Carbachol (10 μm) elicited a transient increase of intracellular calcium with greater increment in tracheal smooth muscle cells from bleomycin-exposed rats compared with controls (372 ± 42 nmvs. 176 ± 20 nm; n = 7, P < 0.01). 5 Circulating plasma levels of TNF-α/IL-1β were augmented in bleomycin-exposed rats compared with controls. Tissue incubation with TNF-α (100 ng ml−1)/IL-1β (10 ng ml−1) increased in vitro tracheal responsiveness to carbachol. 6 In conclusion, tracheal contraction in response to muscarinic receptor stimulation with carbachol was increased in bleomycin-exposed rats. This in vitro cholinergic hyperresponsiveness may be related to the augmented levels of inflammatory cytokines in bleomycin-exposed rats.

year	journal	country	edition	language
2006-08-02	Autonomic and Autacoid Pharmacology

https://doi.org/10.1111/j.1474-8673.2006.00378.x