Abstract 20669: Urocortin-2 Improves Right Ventricular Function in Pulmonary Arterial Hypertension

Abstract

Introduction: Urocortin (UCN)-2 is a peptide highly expressed in the cardiovascular system and it has shown promising therapeutic effects in several studies in both humans and animal models of heart failure (HF). However, the role of UCN-2 in right ventricular (RV) failure is still unknown. Hypothesis: This study analyzed the effects of UCN-2 treatment in an animal model of RV HF, secondary to pulmonary arterial hypertension (PAH). Methods: Male Wistar rats (180-200g) randomly received monocrotaline (MCT, 60mg/Kg, s.c.) or vehicle. After 14 days, animals from these groups were randomly assigned to receive treatment with either UCN-2 (2.5μg/Kg/day, i.p.) or vehicle. The study resulted in 4 groups: control (CTRL) (n=12); CTRL+UCN-2 (n=10); MCT (n=9); MCT+UCN-2 (n=8). RV Pressure-Volume measurements were performed 24-25 days after MCT administration. Only significant results (mean±SEM, p<0.05) are given. Results: MCT group developed PAH, as shown by: increased RV end-systolic pressure (MCT vs CTRL: 59±3 vs 26±1 mmHg) and end-diastolic pressure (MCT vs CTRL: 6.7±0.9 vs 3.5±0.7 mmHg), RV dilatation (MCT vs CTRL: 270±17 vs 215±12 μL), and decreased cardiac output (MCT vs CTRL: 29±3 vs 63±3 mL/min) and ejection fraction (MCT vs CTRL: 37±6 vs 72±2%). UCN-2 treatment resulted in attenuation of RV pressure increase (RVESP: 42±2 mmHg; RVEDP: 4.7±0.6 mmHg), dilatation (RVEDV: 212±4 μL), and in improved cardiac function (CO: 48±2 mL/min; EF: 58±2%). Conclusions: UCN-2 chronic treatment significantly reduced the worsening of RV function in PAH. These findings suggest that the UCN-2 pathway has a relevant role on the pathophysiology of PAH and RV failure, representing a potential therapeutic target.