Effects of levosimendan on cardiac remodeling and cardiomyocyte apoptosis in hypertensive Dahl/Rapp rats

Background and purpose: Progression of heart failure in hypertensive Dahl rats is associated with cardiac remodeling and increased cardiomyocyte apoptosis. This study was conducted to study whether treatment with a novel inotropic vasodilator compound, levosimendan, could prevent hypertension‐induced cardiac remodeling and cardiomyocyte apoptosis. Experimental approach: 6‐week‐old salt‐sensitive Dahl/Rapp rats received levosimendan (0.3 mg kg‐1 and 3 mg kg‐1 via drinking fluid) and high salt diet (NaCl 7%) for 7 weeks, Dahl/Rapp rats on low‐salt diet served as controls. Blood pressure, cardiac functions by echocardiography, cardiomyocyte apoptosis by TUNEL technique, tissue morphology, myocardial expression of calcium cycling proteins, and markers of neurohumoral activation were determined. Key Results: Untreated Dahl/Rapp rats on high salt diet developed severe hypertension, cardiac hypertrophy and moderate systolic dysfunction. 38% of Dahl/Rapp rats (9/24) survived the 7‐week‐follow‐up period. Cardiomyocyte apoptosis was increased by 6‐fold during high salt diet. Levosimendan improved survival (survival rates in low‐ and high‐dose levosimendan groups 12/12 and 9/12, p