Abstract 19600: Inhibition of Increased Thrombin Receptor Activity Attenuated Monocrotaline-induced Pulmonary Hypertension in Rats

Background and Objectives: Thrombin contracts the normal pulmonary artery (PA), while it relaxes the normal systemic artery endothelium-dependently. This unique property of pulmonary artery may contribute to the pathogenesis of pulmonary artery hypertension (PAH), because it frequently associated with thrombus formation and thrombotic pulmonary arteriopathy. However, the responsiveness to thrombin and its role in PAH remain unknown. We investigated, in monocrotaline (MCT)-induced PH in rats, the contractile responsiveness to thrombin and explored a therapeutic potential of antagonizing the thrombin receptors. Methods and Results: Three weeks after a single subcutaneous injection of MCT (60 mg/kg), MCT increased right ventricular (RV) systolic pressure (SP) (Normal: 23±3 vs. MCT: 74±4 mmHg, n=6~10, p Conclusions: This study provides the first evidence that the contractile response of PA to thrombin is increased in PAH. We conclude that antagonizing the increased thrombin receptor activity in PAH may serve as a novel therapeutic target.