β-blockers of the Third Generation Inhibit Endothelin-1 Liberation, mrna Production and Proliferation of Human Coronary Smooth Muscle and Endothelial Cells

Endothelin-1 (ET-1) plays an important role in atherogenesis. The aim of the study reported here was to investigate the effects of the third generation β-blockers nebivolol and carvedilol on ET-1 liberation, preproendothelin-1 production and on proliferation of human coronary cells. Human coronary endothelial (HEC) and smooth muscle cells (HCSMC) were grown with carvedilol or nebivolol (10 -7 -10 -5 mol/l). Incubation for 1, 2 or 7 days resulted in an 80% concentration- and time-dependent reduction in HCSMC proliferation. β-blockers such as propranolol or metoprolol did not influence cell proliferation. Nebivolol (10 -7 mol/l) inhibited accelerated HCSMC proliferation in the presence of growth factors such as transforming growth factor-β1 or platelet-derived growth factor BB. During incubation with nebivolol or carvedilol ET-1 secretion decreased. For nebivolol this is a result of a reduction in preproendothelin-1 mRNA levels. β-blockers of the third generation that reduce the cell proliferation and ET-1 secretion may represent strategies with great promise for antiproliferative therapy of coronary heart disease.