Effect of sildenafil on acrolein-induced airway inflammation and mucus production in rats
| Autor: | Duan Yp, Lin J, Wang X, Liu Y, Fuqiang Wen, Liu Ds, Xuemei Ou, Ting-Hua Wang, Luonan Chen, Hu Xr, Dan Xu, Yulin Feng |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Lung Diseases
Male Pulmonary and Respiratory Medicine medicine.medical_specialty medicine.drug_mechanism_of_action Sildenafil Blotting Western Enzyme-Linked Immunosorbent Assay Respiratory Mucosa Nitric Oxide Bronchoalveolar Lavage Piperazines Sildenafil Citrate Nitric oxide Rats Sprague-Dawley chemistry.chemical_compound Internal medicine Leukocytes Animals Medicine Sulfones Acrolein Cyclic GMP Inflammation Analysis of Variance Goblet cell medicine.diagnostic_test Reverse Transcriptase Polymerase Chain Reaction business.industry Mucin Mucins Phosphodiesterase respiratory system Immunohistochemistry Mucus Rats respiratory tract diseases Endocrinology Bronchoalveolar lavage medicine.anatomical_structure chemistry Purines Cytokines business Phosphodiesterase 5 inhibitor |
| Zdroj: | European Respiratory Journal. 33:1122-1132 |
| ISSN: | 1399-3003 0903-1936 |
| DOI: | 10.1183/09031936.00055908 |
| Popis: | Airway inflammation with mucus overproduction is a distinguishing pathophysiological feature of many chronic respiratory diseases. Phosphodiesterase (PDE) inhibitors have shown anti-inflammatory properties. In the present study, the effect of sildenafil, a potent inhibitor of PDE5 that selectively degrades cyclic guanosine 3',5'-monophosphate (cGMP), on acrolein-induced inflammation and mucus production in rat airways was examined. Rats were exposed to acrolein for 14 and 28 days. Sildenafil or distilled saline was administered intragastrically prior to acrolein exposure. Bronchoalveolar lavage fluid (BALF) was acquired for cell count and the detection of pro-inflammatory cytokine levels. Lung tissue was examined for cGMP content, nitric oxide (NO)-metabolite levels, histopathological lesion scores, goblet cell metaplasia and mucin production. The results suggested that sildenafil pretreatment reversed the significant decline of cGMP content in rat lungs induced by acrolein exposure, and suppressed the increase of lung NO metabolites, the BALF leukocyte influx and pro-inflammatory cytokine release. Moreover, sildenafil pretreatment reduced acrolein-induced Muc5ac mucin synthesis at both mRNA and protein levels, and attenuated airway inflammation, as well as epithelial hyperplasia and metaplasia. In conclusion, sildenafil could attenuate airway inflammation and mucus production in the rat model, possibly through the nitric oxide/cyclic guanosine 3',5'-monophosphate pathway, and, thus, might have a therapeutic potential for chronic airway diseases. |
| Databáze: | OpenAIRE |
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