Effect of a Soluble Guanylate Cyclase Stimulator on the Purinergic Pathway in an Animal Model of Emphysema Induced by Cigarette Smoke

Abstract Purinergic and nitric oxide (NO) signaling pathways appear to be involved in the development of emphysema and vascular remodeling of chronic obstructive pulmonary disease (COPD). In an animal model, we evaluate the gene and protein expression of ENTPD1/CD39 and NT5E/CD73, and the effect on this expression of a guanylate cyclase (GC) stimulator. Forty-two guinea pigs underwent sham exposure (SHAM) or cigarette smoke (CS) exposure from three to six months. They were divided into six groups (sham-exposed, smokers or former smokers) and treated with vehicle (VH) or BAY 41-2272 (GC stimulator) for three months. Immunohistochemistry, western blot and qPCR assays were performed on lung tissue samples. Compared to SHAM + VH, ENTPD1 and NT5E were downregulated in the CS + VH group (1 ± 0 vs. 0.78 ± 0.51, p > 0.05, and 1 ± 0 vs. 0.45 ± 0.27, p = 0.027 respectively). Treatment with BAY 41-2722 increased ENTPD1 and NT5E expression to 1.06 ± 0.4 and 0.71 ± 0.35, respectively. No changes in the Ex-CS + BAY group were found. NT5E/CD73 was downregulated in the lungs of an animal model of emphysema. Treatment with a soluble GC stimulator tended to restore the gene and protein expression of ENTPD1/CD39 and NT5E/CD73 in smoke-exposed animals, suggesting its implication in a new mechanism for preventing emphysema.