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Sibutramine is a serotonin-noradrenaline reuptake inhibitor that is effective for long-term weight reduction and maintenance in obese patients when used as an adjunct to dietary and behavioural measures. Because the inhibition of noradrenaline reuptake may be expected to increase systolic and diastolic blood pressure (SBP and DBP) and pulse rate (PR), a 12-week multi-centre, placebo-controlled, double-blind study was designed to evaluate the efficacy and tolerability of sibutramine for weight loss in obese patients whose hypertension was well controlled (DBP р95 mm Hg) by ␤-adrenergic blocking agents (␤-blockers), with or without concomitant thiazide diuretics. Of the 61 patients randomised to sibutramine 20 mg once daily or placebo, 55 patients (90%) completed the study. After 12 weeks, sibutramine-treated patients lost significantly more weight than placebo-treated patients: mean weight reductions were 4.2 kg (4.5%) in the sibutramine group vs 0.3 kg (0.4%) in the placebo group (P Ͻ0.001). Greater weight reduction on sibutramine was accompanied by trends for greater mean reductions in serum triglycerides and very low density lipoprotein cholesterol. Sibutramine was well tolerated, and most adverse events were mild or moderate in severity. No sibutramine patient discontinued treatment because of an adverse event. Mean supine and standing DBP and SBP were not

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Efficacy and safety of sibutramine for weight loss in obese patients with hypertension well controlled by β-adrenergic blocking agents: a placebo-controlled, double-blind, randomised trial

Sramek

Leibowitz

Weinstein

et al. 2002

J Hum Hypertens

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

André

Arnet

Yang

et al. 2000

Journal of Cardiovascular Pharmacology

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An enhanced vasoconstriction and vascular smooth muscle cell proliferation are involved in pathogenesis of hypertension. Beta3-blockers are effective for treatment of hypertensive patients. Recently the new beta1-receptor blocker nebivolol showed a different hemodynamic profile from those of other classic beta-blockers. In this study we hypothesized that nebivolol may also have different effects on smooth muscle cell proliferation compared with other beta-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 (p42mapk) and S6-kinase (p70S6K) and cell-cycle regulatory proteins (i.e., Cdk2, p27Kip1, 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 x 10(3)/well), which was inhibited by nebivolol (10(-8)-10(-5) M; 25 +/- 2 x 10(3)/well; n = 6; p < 0.05), but not by atenolol. 5% FCS activated p42mapk, S6K, and Cdk2, but downregulated p27Kip1 and hyperphosphorylated pRb. Nebivolol prevented Cdk2 activation without influencing p42mapk, S6K, pRB, and p27Kip1. Thus, the new beta1-blocker nebivolol exhibits antiproliferative effect on human SMC through inactivation of Cdk2. This effect of nebivolol may have advantages over other beta-blockers in treatment of patients with cardiovascular disease.

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β-Blockade in Hypertension and Congestive Heart Failure

Ambrosioni

Bacchelli²,

Esposti³

et al. 2001

Journal of Cardiovascular Pharmacology

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Controversy

Abstract: In the single-blind Medical Research Council's (MRC) trial, first published in 1985, 17 354 adult patients with

Cited by 11 publications

References 45 publications

Efficacy and safety of sibutramine for weight loss in obese patients with hypertension well controlled by β-adrenergic blocking agents: a placebo-controlled, double-blind, randomised trial

Efficacy and safety of sibutramine for weight loss in obese patients with hypertension well controlled by β-adrenergic blocking agents: a placebo-controlled, double-blind, randomised trial

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

β-Blockade in Hypertension and Congestive Heart Failure

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