Soluble guanylate cyclase stimulation reduces oxidative stress in experimental Chronic Obstructive Pulmonary Disease

• Published in: PloS one 2018-01, Vol.13 (1), p.e0190628-e0190628
• Main Authors: Paul, Tanja, Salazar-Degracia, Anna, Peinado, Victor I, Tura-Ceide, Olga, Blanco, Isabel, Barreiro, Esther, Barberà, Joan A
• Format: Article
• Language: English
• Subjects: 4-Hydroxynonenal; 8-Hydroxydeoxyguanosine; Airspace; Analysis; Animal models; Animals; Biology and Life Sciences; Biomarkers; Biomedical research; Body weight; Body weight gain; Cell size; Chronic obstructive lung disease; Chronic obstructive pulmonary disease; Cigarette smoke; Complications and side effects; Cyclic GMP; Development and progression; Disease; Drugs; Emphysema; Enzymes; Exposure; Genetic aspects; Guanosine; Guanylate cyclase; Guinea pigs; Hospitals; Inflammation; Inflammatory response; Laboratories; Lung cancer; Lung diseases; Lungs; Malalties de l'aparell respiratori; Medicaments; Medicine; Medicine and Health Sciences; Musculoskeletal system; Nitric oxide; Obstructive lung disease; Oxidation; Oxidative stress; Physiological aspects; Plasma levels; Proteins; Research and Analysis Methods; Respiratory diseases; Respiratory organs diseases; Signal transduction; Smoke; Smoking; Smooth muscle; Stimulation; Stimulators; Tyrosine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0190628

Soluble guanylate cyclase (sGC) is a key enzyme of the nitric oxide-cyclic guanosine 3',5'-monophosphate (NO-cGMP) signaling pathway, and its pharmacological stimulation has been shown to prevent the development of emphysema and pulmonary vascular remodeling in animal models of chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the effects of sGC stimulation on oxidative stress in the plasma of guinea pigs chronically exposed to cigarette smoke (CS). Guinea pigs were exposed to CS or sham for three months, and received either the sGC stimulator BAY 41-2272 or vehicle. Body weight was measured weekly; and markers of oxidative stress in plasma, and airspace size and inflammatory cell infiltrate in lung tissue were analyzed at the end of the study. Compared to sham-exposed guinea pigs, CS-exposed animals gained less body weight and showed higher plasma levels of nitrated tyrosine residues (3-NT), 4-hydroxynonenal (4-HNE), and 8-hydroxydeoxyguanosine (8-OHdG). Treatment with the sGC stimulator led to a body weight gain in the CS-exposed guinea pigs similar to non-exposed and attenuated the increase in 3-NT and 4-HNE. Plasma levels of 3-NT correlated with the severity of inflammatory cell infiltrate in the lung. Stimulation of sGC prevents oxidative stress induced by CS exposure and is associated with an attenuated inflammatory response in the lung.