title: Reduced immunoreactivities of B-type natriuretic peptide in pulmonary arterial hypertension rats after ranolazine treatment.
abstract: Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by sustained increase in the pulmonary arterial pressure and excessive thickening and remodeling of the distal small pulmonary arteries. During disease progression, structural remodeling of the right ventricular (RV) impairs pump function, creates pro-arrhythmic substrates and triggers for arrhythmias. Notably, RV failure and lethal arrhythmias are major contributors to cardiac death in PAH that are not directly addressed by currently available therapies. Ranolazine (RAN) is an anti-anginal, anti-ischemic drug that has cardioprotective effects of heart dysfunction. RAN also has anti-arrhythmic effects due to inhibition of the late sodium current in cardiomyocytes. Therefore, we hypothesized that RAN could reduce the mal-adaptive structural remodeling of the RV, and prevent triggered ventricular arrhythmias in the monocrotaline-induced rat model of PAH. RAN reduced ventricular hypertrophy, reduced levels of B-type natriuretic peptide, and decreased the expression of fibrosis. In addition, RAN prevented cardiovascular death in rat model of PAH. These results support the notion that RAN can improve the functional properties of the RV, highlighting its potential benefits in the setting of heart impairment.
authors.affiliation: Department of Biology, School of Life Sciences, Chungbuk National University, Cheongju, Korea.; Department of Surgery, Brain Korea 21 PLUS Project for Medical Sciences and HBP Surgery and Liver Transplantation, Korea University College of Medicine, Seoul, Korea.; Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea.; Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Jae Chul
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Kwan Chang
authors.initials: KC
authors.lastname: Kim
authors.affiliation: Department of Biology, School of Life Sciences, Chungbuk National University, Cheongju, Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choe
authors.affiliation: Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Hong
keywords: B-type natriuretic peptide; Heart; Pulmonary artery hypertension; Ranolazine; Right ventricles