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 the study reported here was to investigate the effects of the third generation beta-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. beta-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-beta1 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. 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 coronary heart disease.
Brehm
B R
BR
Medical Clinic III, University of Tuebingen, Germany. 101566.341@compuserve.com
Bertsch
D
D
von Fallois
J
J
Wolf
S C
SC
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D004983:Ethanolamines / Q000494:pharmacology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D000068577:Nebivolol; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D019332:Endothelin-1; D004983:Ethanolamines; D016212:Transforming Growth Factor beta; D000068577:Nebivolol