RT Journal Article SR Electronic T1 The role of guanylyl cyclase in resistive breathing JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 385 VO 42 IS Suppl 57 A1 Constantinos Glynos A1 Dimitris Toumpanakis A1 Constantinos Loverdos A1 Vassiliki Karavana A1 Zongmin Zhou A1 Maria Dettoraki A1 Tatiana Michailidou A1 Christina Magkou A1 Stamatios Theocharis A1 Andreas Papapetropoulos A1 Charis Roussos A1 Theodoros Vassilakopoulos YR 2013 UL http://erj.ersjournals.com/content/42/Suppl_57/385.abstract AB INTRODUCTION: Resistive breathing (RB) due to airflow limitation is the pathophysiologic hallmark of the chronic obstructive pulmonary disease (COPD). Smooth muscle tone constitutes an important determinant of airflow limitation. The principal pathway for smooth muscle tone involves nitric oxide (NO) signalling through activation of the soluble guanylyl cyclase (sGC). We aim to investigate the expression and downstream signalling of sGC in RB. METHODS: C57BL/6 wild type and sGC α 1 -/- mice underwent RB by placing a nylon band around the extrathoracic trachea segment, providing a 50% tracheal occlusion. Animals were divided into groups: 1. Mice with tracheal banding (TB) for 24 hrs and sham operated (control) mice. 2. sGC-α 1 -/- TB and control mice, 3. TB and control mice treated with inhaled sGC inhibitor, (ODQ; 20mg/Kg), 4. TB and control mice treated with sGC activator, BAY 58-2667(10µg/Kg; ip). RESULTS: Mice subjected to TB, exhibited a significant increase in BALF cellularity and protein content, consistent with acute inflammation. Using a forced oscillation technique, TB resulted in increased tissue elasticity and airway resistance and downward shift of the pressure-volume curve. TB reduced the expression of both α1 and β1 subunits of sGC, at mRNA and protein level, in the lung. A pronounced inflammation occurred after further reduction of sGC activity by ODQ or in sGC α 1 -/- mice. Pharmacological activation of sGC, using BAY 58-2667, 30 min before or 24 hrs after TB, reversed the injurious effects of RB on the lung. CONCLUSIONS: Our model of TB might offer new insights into a potentially protective role of the sGC in the context of resistive breathing.