Nebivolol Inhibits Human Aortic Smooth Muscle Cell Growth: Effects on Cell Cycle Regulatory Proteins

An enhanced vasoconstriction and vascular smooth muscle cell proliferation are involved in pathogenesis of hypertension. β-Blockers are effective for treatment of hypertensive patients. Recently the new β1-receptor blocker nebivolol showed a different hemodynamic profile from those of other classic...

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Veröffentlicht in:Journal of cardiovascular pharmacology 2000-06, Vol.35 (6), p.845-848
Hauptverfasser: André, Dominique E, Arnet, Urs, Yang, Zhihong, Lüscher, Thomas F
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Sprache:eng
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Zusammenfassung:An enhanced vasoconstriction and vascular smooth muscle cell proliferation are involved in pathogenesis of hypertension. β-Blockers are effective for treatment of hypertensive patients. Recently the new β1-receptor blocker nebivolol showed a different hemodynamic profile from those of other classic β-blockers. In this study we hypothesized that nebivolol may also have different effects on smooth muscle cell proliferation compared with other β-blockers such as atenolol. Human aortic smooth muscle cells (SMCs) were cultured, and cell growth was determined by increase in cell number. Growth-signaling molecules such as mitogen-activated protein kinase (p42) and S6-kinase (p70) and cell-cycle regulatory proteins (i.e., Cdk2, p27, and pRb) were analyzed by immunoblotting. In cultured human aortic SMCs, cell number was markedly increased in response to 5% fetal calf serum (FCS) over 6 days (87 ± 11 × 10/well), which was inhibited by nebivolol (10−10 M; 25 ± 2 × 10/well; n = 6; p < 0.05), but not by atenolol. 5% FCS activated p42, S6K, and Cdk2, but downregulated p27 and hyperphosphorylated pRb. Nebivolol prevented Cdk2 activation without influencing p42, S6K, pRB, and p27. Thus, the new β1-blocker nebivolol exhibits antiproliferative effect on human SMC through inactivation of Cdk2. This effect of nebivolol may have advantages over other β-blockers in treatment of patients with cardiovascular disease.
ISSN:0160-2446
1533-4023
DOI:10.1097/00005344-200006000-00003