RGD Reference Report - Effect of sildenafil on acrolein-induced airway inflammation and mucus production in rats. - Rat Genome Database

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Effect of sildenafil on acrolein-induced airway inflammation and mucus production in rats.

Authors: Wang, T  Liu, Y  Chen, L  Wang, X  Hu, XR  Feng, YL  Liu, DS  Xu, D  Duan, YP  Lin, J  Ou, XM  Wen, FQ 
Citation: Wang T, etal., Eur Respir J. 2009 May;33(5):1122-32. Epub 2009 Jan 7.
RGD ID: 2314463
Pubmed: PMID:19129291   (View Abstract at PubMed)
DOI: DOI:10.1183/09031936.00055908   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Inflammation  ISOPde5a (Rattus norvegicus)2314463; 2314463 RGD 
Inflammation  IMP 2314463 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of chronic inflammatory response  IMP 2314463 RGD 
short-term memory  IMP 2314463 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pde5a  (phosphodiesterase 5A)

Genes (Mus musculus)
Pde5a  (phosphodiesterase 5A, cGMP-specific)

Genes (Homo sapiens)
PDE5A  (phosphodiesterase 5A)


Additional Information