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

Abstract

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.