beta-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 th e study reported here was to investigate the effects of the third generatio n beta -blockers nebivolol and carvedilol on ET-1 liberation, preproendothe lin-1 production and on proliferation of human coronary cells. Human corona ry endothelial (HEC) and smooth muscle cells (HCSMC) were grown with carved ilol or nebivolol (10(-7)-10(-5) mol/l). incubation for 1, 2 or 7 days resu lted in an 80% concentration- and time-dependent reduction in HCSMC prolife ration. beta -blockers such as propranolol or metoprolol did not influence cell proliferation. Nebivolol (10(-7) mol/l) inhibited accelerated HCSMC pr oliferation in the presence of growth factors such as transforming growth f actor-beta1 or platelet-derived growth factor BB. During incubation with ne bivolol or carvedilol ET-1 secretion decreased. For nebivolol this is a res ult of a reduction in preprolndothelin-1 mRNA levels. beta -blockers of the third generation that reduce the cell proliferation and ET-1 secretion may represent strategies with great promise for antiproliferative therapy of c oronary heart disease.