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

¹ Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, and Dept of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China
² Dept of Biochemistry, Tibet University Medical College, Lhasa, Tibet 850002, China

^* To whom correspondence should be addressed. E-mail: wenfuqiang.scu{at}gmail.com,.

	Abstract

Airway inflammation with mucus overproduction is a distinguishing pathophysiological feature of many chronic respiratory diseases. Phosphodiesterase (PDE) inhibitors have shown anti-inflammatory properties. In this study, we examined the effect of sildenafil, a potent inhibitor of PDE5 that selectively degrades cGMP, on acrolein-induced inflammation and mucus production in rat airways.

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 detection of proinflammatory cytokine levels. Lung tissue was examined for cGMP content, nitric oxide (NO)-metabolite levels, histopathologic 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 proinflammatory cytokine release. Moreover, sildenafil pretreatment reduced the 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 NO/cGMP pathway, and, thus, might have therapeutic potential for chronic airway diseases.