Therapeutic sildenafil inhibits pulmonary damage induced by cigarette smoke exposure and bacterial inhalation in rats

CONTEXT: Clinical reports showed sildenafil beneficial therapy on severe chronic obstructive pulmonary disease (COPD) with pulmonary hypertension (PH) patients. OBJECTIVE: The study investigated therapeutic effects of silenafil on pulmonary damage induced by cigarette smoke exposure and bacterial inhalation in rats. MATERIALS AND METHODS: Female Sprague-Dawley rats (200–250 g) were divided into control group (no exposure, n = 10) and exposure group (n = 50) suffered from cigarette smoke exposure and Klebsiella pneumonia inhalation for 8 weeks. Then rats were orally given normal saline (control group or model group), 2.0, 3.0, or 4.5 mg/kg sildenafil for 4 weeks, respectively. Pulmonary pressure, RVHI and morphological analysis of pulmonary vascular remodeling, respiratory functions assay, morphological analysis of pulmonary alveoli, and expression of PCNA and caspase-3 of epithelial cells in bronchioles wall were examined. RESULTS: Compared to model rats, 2.0, 3.0, and 4.5 mg/kg sildenafil increased VT by –0.6 to 9.58%, PEF by 3.12 to 6.49%, EF50 by 0.81 to 6.50%, decreased mPAP by 4.43 to 25.58%, RVHI by 6.54 to 26.41%, showing a dose-dependent improvement. Furthermore, 4.5 mg/kg sildenafil significantly increased MAN by 39.70%, LA/CSA by 37.07%, decreased muscular pulmonary arteries by 48.00%, WT by 12.83%, MT by 22.89%, caspase-3 expression by 17.71%, and showed improvement on abnormality in lung interstitial and bronchioles by microscopy. DISCUSSION AND CONCLUSION: Our results demonstrated that sildenafil decreased pathological changes in alveoli, bronchioles, interstitial tissue, and arterioles of rats with COPD and PH.