Disease relevance of Nebivolol

• Effects of nebivolol in elderly heart failure patients with or without systolic left ventricular dysfunction: results of the SENIORS echocardiographic substudy [1].
• Nebivolol in hypertension and chronic heart failure: a viewpoint by alberto zanchetti [2].
• Cardiac hypertrophy and collagen content both in heart and aorta were significantly reduced, and these changes persisted after nebivolol suppression [3].
• Nebivolol improves coronary flow reserve in hypertensive patients without coronary heart disease [4].
• CONCLUSION: The nebivolol antihypertensive effect was accompanied by an important reduction of hypertrophy and collagen deposition in both vascular and left ventricle tissue, which was maintained after a long period of therapy withdrawal [3].

High impact information on Nebivolol

• Nebivolol and its 4-keto derivative increase nitric oxide in endothelial cells by reducing its oxidative inactivation [5].
• OBJECTIVES: The objective of the present study was to elucidate the vasodilator mechanisms of nebivolol, a high selective beta(1)-receptor antagonist with antioxidant properties [5].
• The preincubation of BAECs with blocking anti-LOX-1 monoclonal antibody (LOX-1 mAb) significantly counteracted the effect of ox-LDL on stimulated generation of NO (p < 0.001), but the effect was significantly lower than that of nebivolol and its 4-keto derivative alone (p < 0.01) [5].
• Despite a decrease in heart rate with nebivolol, there was a slight decrease in left ventricular end-diastolic volume (p = NS) [6].
• Exercise time, invasive hemodynamic data (12- and 24-h monitoring) and variables of left ventricular function were examined at baseline and after 3 months of orally administered nebivolol (1 to 5 mg/day, n = 11) or placebo (n = 13) [6].

Chemical compound and disease context of Nebivolol

• OBJECTIVE : To investigate whether chronic selective beta1-blockade with nebivolol could prevent endothelial dysfunction in salt-induced hypertension, and to compare it with atenolol [7].
• METHODS: One day after induction of anti-thy1 glomerulonephritis, rats were given increasing doses of the beta-blockers metoprolol or nebivolol (0.1-fold, one-fold, 10-fold and 20-fold of the known blood pressure dose) until day 6 and the 20-fold dose until day 12 [8].
• We provided evidence that nebivolol, given as monotherapy or in combination with low dose of hydrochlorothiazide, is effective in reducing clinic and 24-h ambulatory blood pressure in patients with ambulatory hypertension [9].
• After a washout period of 8 weeks, 51 patients with mild to moderate essential hypertension were randomized to double-blind treatment with either nebivolol 5 mg once a day (n = 26) or nifedipine sustained-release 20 mg bid (n = 25) over a period of 12 weeks [10].
• METHODS: In a double-blind, randomized, parallel group study 314 patients with hypertension were treated for 12 weeks with 5 mg of nebivolol or 50 mg of losartan once daily [11].

Biological context of Nebivolol

• Nebivolol improved stroke volume, ejection fraction and left ventricular end-diastolic pressure, not through a measurable reduction in afterload or a lusitropic effect, but by improving systolic contractile performance [6].
• Beta-blockade with nebivolol enhances the acetylcholine-induced cutaneous vasodilation [12].
• Nebivolol bound to S1A binding sites with a Ki value of 20 nM [13].
• RESULTS: In hypertensive patients, nebivolol and atenolol significantly reduced blood pressure values after 4 weeks of treatment [14].
• Nebivolol decreases oxidative stress in essential hypertensive patients and increases nitric oxide by reducing its oxidative inactivation [14].

Anatomical context of Nebivolol

• Nebivolol is a selective beta(1)-adrenoceptor blocker that has a vasorelaxant activity thought to be the result of a facilitation of the release of nitric oxide from the endothelium [12].
• Celiprolol and nebivolol caused vasodilation in the rat thoracic aorta, and it was markedly reduced by endothelial denudation, Nomega-nitro-L-arginine methyl ester (10(-4) mol/L), or NAN-190 (10(-6) mol/L) [15].
• CONCLUSIONS: In hypertensive patients free of coronary artery disease, 4-week nebivolol therapy induces a significant increase of the CFR [4].
• The aim of this study was to investigate the effects of the new beta-blocker nebivolol on cell proliferation of human coronary smooth muscle cells (haCSMCs) and endothelial cells (haECs) in comparison to traditional beta-blockers [16].
• Characterization of beta(1)-selectivity, adrenoceptor-G(s)-protein interaction and inverse agonism of nebivolol in human myocardium [17].

Associations of Nebivolol with other chemical compounds

• The subjects were randomly allocated to an 8-day treatment with nebivolol (5 mg once a day) and atenolol (50 mg once a day) according to a cross-over design [12].
• RESULTS: At the end of treatment, nebivolol and metoprolol significantly decreased blood pressure and heart rate, with a more pronounced bradycardic effect of metoprolol [18].
• Standing blood pressure and/or mean 24-hour ambulatory blood pressure is significantly and similarly reduced with nebivolol, atenolol or nifedipine [19].
• In COS-7-cells, beta(1)-selectivity is 3 fold for nebivolol and 15 fold for bisoprolol [17].
• Nebivolol and atenolol had nearly identical cardiovascular profiles, which were much more beta-1 selective than that of propranolol [heart rate and blood pressure ID50 values, mg/kg: 0.034, 0.036 (propranolol); 0.058, 0.713 (nebivolol); 0.047, 0.506 (atenolol)] [20].

Gene context of Nebivolol

• Nebivolol is a highly selective beta1-adrenoreceptor-blocking agent with a peculiar pharmacodynamic profile [21].
• Beta1- or beta2-Adrenoreceptor antagonists do not inhibit the action of nebivolol [21].
• In a mouse aortic ring assay of neoangiogenesis, nebivolol induced neocapillary tube formation in rings from wild-type but not beta3-adrenoreceptor- or endothelial NOS-deficient mice [22].
• Because the vascular NADPH oxidase is an important superoxide source, we studied the effect of nebivolol on endothelial function and NADPH oxidase activity and expression in the well-characterized model of angiotensin II-induced hypertension [23].
• In vitro treatment with nebivolol but not atenolol or metoprolol induced a dissociation of p67(phox) and Rac1, as well as an inhibition of NADPH oxidase activity assessed in heart membranes from angiotensin II-infused animals, as well as in homogenates of Nox1 and cytosolic subunit-transfected and phorbol ester-stimulated HEK293 cells [23].

Analytical, diagnostic and therapeutic context of Nebivolol

• Cardiovascular effects of nebivolol in spontaneously hypertensive rats persist after treatment withdrawal [3].
• This paper proves that HPLC at high pH combined with on-line diode-array detection is an excellent technique for the location of the hydroxyl functions in hydroxylated metabolites of nebivolol [24].
• Published randomized, controlled, multicenter studies with nebivolol have shown that once-daily treatment significantly reduces systolic and diastolic blood pressure in patients with mild-to-moderate hypertension, compared with placebo, in a dose-dependent manner, and is well tolerated, with an adverse event profile similar to that of placebo [25].
• Effect of forced titration of nebivolol on response rate in obese hypertensive patients [26].
• To investigate whether in vivo metabolized nebivolol retains high beta(1)-adrenoceptor selectivity, serum specimens were collected before and 2 h after oral administration of 5 mg nebivolol [27].

References