Abstract P2037: Activation Of A2A Adenosine Receptor Reduces Cardiac Dysfunction Resulting From Pulmonary Hypertension In Rats

Pulmonary hypertension (PH) is characterized by extensive pulmonary vascular remodeling, leading to right ventricle (RV) hypertrophy and dysfunction. This work evaluates the hypothesis that the activation of adenosine A2A receptor (AR-A2) by LASBio-1900 could interfere with the cardiac and vascular dysfunction on monocrotaline (MCT)-induced PH in rats. After 14 days of PH induction using a single injection of MCT (60 mg/kg i.p.), twelve male Wistar rats were randomly divided in groups and treated orally either with vehicle or LASSBio-1900 (180 μmol/kg/day). Hemodynamic parameters were obtained using the echocardiography and summarized in table 1. LASSBio-1900 reduced RV hypertrophy observed in PH because the Fulton index altered from 55.4 ± 2.3 to 35.3 ± 5.9% (p<0.05). HP increased RV systolic and diastolic pressure from 19.2 ± 2.0 and 4.7 ± 1.0 to 51.5 ± 5.2 and 11.9 ± 1.3 mmHg, respectively. Ventricular dysfunction was recovered with LASSBio-1900 treatment reducing pressures to 28.4 ± 4.0 and 6.5 ± 0.8 mmHg, indicating improvement of RV dysfunction. Pulmonary arteriole (PA) muscularization was evaluated by alpha- smooth muscle actin stained and vessel medial wall area was expressed as the percentage of the portion positively stained relative to total transversal area. The increase of the wall thickness of distal PA from 61.7 ± 1.1 to 83.24 ± 1.82 % was reduced by LASSBio-1900 (75.2 ± 3.4 %). Perivascular collagen in PA was evaluated through picrosirius red staining and interstitial fibrosis was measured by obtaining the total collagen area per arteriole area. PH increased the perivascular collagen deposition in 15.1 ± 1.3% however, treatment with LASSBio-1900 reduced to 8.7 ± 1.4% (p<0.05). Intense inflammation process on PH was confirmed with the increase of iNOS expression from 4.5 ± 0.3 (control) to 19.0 ± 0.9% (p<0.05) with reduction to 8.7 ± 1.4% when treated with LASSBio-1900. In conclusion, the agonist of AR-A2, named LASSBio-1900 improved RV function and pulmonary structural alteration in PH, indicating a new alternative for treatment of PH-induced RV dysfunction.