TY - JOUR T1 - Elevated levels of adenosine in the lungs lead to chronic lung injury and pulmonary hypertension JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p3347 AU - Harry Karmouty-Quintana AU - Hongyan Zhong AU - Dewan Zeng AU - Luiz Belardinelli AU - Michael Blackburn Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p3347.abstract N2 - Pulmonary Hypertension (PH) is characterized by increased pulmonary vascular tone and remodeling of the pulmonary vasculature including muscularization of vessels. PH is often associated with underlying chronic lung diseases (CLD) such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). The adenosine (Ado) A2B receptor (R) expression is increased in patients with COPD and IPF. Activation of the A2BR by Ado has been shown to regulate fibrosis through its action in inflammatory and structural cells. However, the role of Ado and the A2BR in the pathogenesis of PH is not known.Hypothesis: Ado acting on the A2BR modulates the development of PH in CLD.Ado deaminase (ADA)-deficient mice have increased levels of Ado in the lung tissue that lead to CLD. On day 30, once lung injury was established, mice were provided with chow containing placebo or GS-6201, an A2BR antagonist, for the next 10 days. On day 41, right ventricle systolic pressure (RVSP), systemic blood pressure, heart rate and lung function measurements were performed.ADA-deficient mice had increased RVSP compared to control mice. Lung function measurements revealed increased airway resistance and a reduction in airway and tissue compliance in ADA-/- mice. Blockade of the A2BR by GS-6201 inhibited the increased RVSP and restored lung function. No change in systemic systolic blood pressure or heart rate was observed in mice treated with placebo or GS-6201.These results highlight the role of the A2BR in the pathogenesis of PH associated with elevated tissue Ado and CLD. The results suggest that targeting the A2BR could be a potential target for the treatment of PH secondary to CLD. ER -