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The impact of 8-week nebivolol monotherapy on 24-hour blood pressure (BP) monitoring, ECG, autonomic heart regulation, changes in endothelium-dependent vasodilation (EDVD) and endothelium-independent vasodilation, on the plasma concentration of NO metabolites, and on the endothelial responsiveness index (ERI) were studied in 30 patients with stages I-II AH.
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This study assessed blood pressure (BP) reductions and response rates following addition of nebivolol to ongoing antihypertensive therapy in patients with uncontrolled stage I-II hypertension despite antihypertensive treatment. Patients with an average sitting diastolic BP (SiDBP) > or =90 and < or =109 mm Hg while taking an antihypertensive regimen were included in this double-blind, placebo-controlled, parallel-group study. The primary efficacy end point was reduction from baseline to week 12 in mean trough SiDBP. In total, 669 patients were randomized to once-daily nebivolol 5, 10 or 20 mg or placebo. Addition of nebivolol 5, 10 and 20 mg significantly reduced BP; placebo-subtracted least squares mean reductions in trough SiDBP were -3.3, -3.5 and -4.6 mm Hg, respectively (P<0.001) and -5.7, -3.7 and -6.2 mm Hg in trough sitting systolic BP (SiSBP), respectively (P< or =0.015). Adding nebivolol 5-20 mg resulted in significantly more responders (SiDBP <90 or > or =10 mm Hg reduction; range: 53.0-65.1 vs 41.3% with placebo; P< or =0.028) and significantly better control rates (SiSBP/SiDBP <140/90 mm Hg; range: 41.3-52.7 vs 29.3% with placebo; P< or =0.029). Nebivolol was well tolerated; the incidence of adverse events with nebivolol was similar to that with placebo (40.2 vs 38.9%, respectively; P=0.763). Addition of once-daily nebivolol to ongoing antihypertensive therapy provided significant additional BP reductions and better response rates in patients with uncontrolled hypertension and was well tolerated.
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Despite a better control in SBP, HR during rest and exercise, and improvement in HRR, nebivolol failed to show a positive effect on peak VO2 and 123I-MIBG scintigraphic parameters. The lack of effect on adrenergic activity may be the cause of the lack of effect on functional capacity.
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Several beta-blocking drugs have been reported to have a beneficial hemodynamic effect in patients with dilated cardiomyopathy, but few data obtained in a placebo-controlled randomized study have addressed the mechanisms of improvement.
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This real-world study suggests that switching from metoprolol to nebivolol is associated with an increase in medication costs and significant reductions in hospitalizations and outpatient visits upon switching, resulting in an overall neutral effect on healthcare costs. These results may be interpreted with caution due to lack of a comparator group and confounding control caused by design and limitations inherent in insurance claims data.
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The aim of the current study was to characterize the effects of the novel β-adrenergic antagonist nebivolol on central aortic blood pressures, arterial properties, and nitroxidergic activity in individuals with prehypertension. Prehypertension is emerging as a major risk factor for several adverse cardiovascular consequences. Increased pulse wave velocity, aortic augmentation index, and aortic blood pressures have been linked with augmented risk of cardiovascular disease and mortality. While the effects of antihypertensive drugs on these parameters in hypertensive patients have been studied, there are limited data so far in prehypertension. Fifty individuals with prehypertension were randomized to either nebivolol (5 mg per day) or placebo in a double-blind clinical trial. Patients underwent measurement of pulse wave velocity as well as aortic blood pressure and aortic augmentation index via pulse wave analysis at baseline and 8 weeks. Patients also had blood and urine biochemistries done at each visit. Nebivolol achieved significant reductions in central aortic systolic (P=.011), diastolic (P=.009), and mean arterial blood pressure (P=.002). Pulse wave velocity trended toward improvement but did not achieve significance (P=.088). Nitric oxide production, measured as urinary nitrite/nitrite excretion, also rose substantially in the nebivolol group (by approximately 60%, P=.030). Central blood pressures can be effectively lowered by β-blockade while patients are still in the prehypertension phase, and the effects may be coupled to improve nitric oxide release by the drug.
At identical degree of β(1)-receptor blockade, metoprolol and nebivolol decreased heart rate to the same extent and preserved cardiac output via increased stroke volume. None of the β-blockers, either after long- or short-term administration, modified LV end-systolic pressure-volume relation. Both β-blockers reduced, after long-term administration, LV end-diastolic pressure, Tau and end-diastolic pressure-volume relation, and this was associated with reduced LV collagen density, but not heart weight. Similar hemodynamic effects were also observed after short-term nebivolol, but not short-term metoprolol. These short-term effects of nebivolol were abolished by NO synthase inhibition. At the vascular level, nebivolol, and to a lesser extend metoprolol, improved NO dependent coronary vasorelaxation, which was abolished by NO synthase inhibition.
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The combination of NEB + HCTZ provided a number of beneficial and additive effects due to the synergistic characteristics of both drugs, in an experimental rat model of hypertension.
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In patients with heart failure and advanced systolic LV dysfunction, nebivolol reduces ventricular size and improves EF. The absence of detectable changes with standard echocardiography in patients with predominant diastolic heart failure questions the mechanism of benefit on morbidity/mortality in such patients.
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Experimental and clinical data on the nephroprotector properties of third-generation beta-adrenoblockers nebivolol and carvedilol are reviewed. These properties are related to the antihypertensive effect and ability of drugs to suppress oxidative stress in glomerules, proximal renal tubules, and surrounding interstitial tissue.
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Nebivolol was not superior to metoprolol in reducing aortic wave augmentation or central BP when combined with HCTZ.
The aim of this study was to investigate the effects of the vasodilating β-blocker nebivolol and the cardioselective β-blocker metoprolol on nitric oxide (NO) levels at vascular graft endothelium and vasa vasorum compared to controls in patients undergoing coronary artery bypass graft surgery.
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Nebivolol is safe and has a similar effect in elderly HF patients with mild or moderate renal impairment.
Disturbed ocular hemodynamics and vasospasms might be involved in the pathogenesis of glaucoma. On a clinical level there are indications for an optimization of ocular perfusion parameters in hypertensive glaucoma patients by switching a beta-adrenoceptor-antagonist therapy to nebivolol. Aim of the present study is to investigate vasoactive properties of nebivolol on ocular vasculature in vitro. Besides vasorelaxing effects, the impact of nebivolol on oxygen free radical-induced vasoconstrictions is studied.
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Forty healthy subjects and 40 matched essential hypertensive patients treated with atenolol and nebivolol according to a double-blind, randomized design participated in the study. Evaluation of brachial artery (BA) reactivity was performed by a longitudinal B-mode scan of the right BA. ADMA and L-arginine were measured by high-performance liquid chromatography. DDAH2 expression and endothelial nitric oxide synthase activity (eNOS) were also evaluated in HUVECs.
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At present in Europe number of deaths due to diseases of cardiovascular system in women has exceeded number of deaths in men. It has been established that process of cardiac remodeling proceeds differently in women and men. This determines different prognosis of the course of chronic heart failure. So after acute myocardial infarction in women more often develops chronic heart failure with preserved systolic left ventricular function while in men prevails chronic heart failure with systolic dysfunction. Substantial differences exist in efficacy of pharmacotherapy: for instance thrombolysis in women is less effective than in men, women are less sensitive to angiotensin converting enzyme inhibitors, administration of digoxin, some antiarrhythmic drugs cause complications in women more often than in men.
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The aim of this study was to compare the effects of the new generation β-blocker anti-hypertensive drugs carvedilol and nebivolol on aortic elastic properties which are important indicators of hypertension-related morbidity and mortality.
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At rest and during exercise, heart rates were as follows: Nebivolol, 57 +/- 7 and 137 +/- 11 beats/min; bisoprolol, 55 +/- 5 and 139 +/- 14 beats/min; carvedilol, 56 +/- 5 and 135 +/- 13 beats/min, with no significant differences between the drugs. Plasma concentrations were as follows: Nebivolol-rest 0.273 +/- 0.029 ng/ml, exercise 0.274 +/- 0.035 ng/ml, recovery 0.272 +/- 0.035 ng/ml (n.s.). Bisoprolol-rest 4.99 +/- 2.73 ng/ml, exercise 6.49 +/- 5.58 ng/ml, recovery 4.90 +/- 3.06 ng/ml ( p < 0.01). Carvedilol-rest 10.3 +/- 9.3 ng/ml, exercise 9.7 +/- 8.2 ng/ml, recovery 6.5 +/- 5.6 ng/ml ( p < 0.05).
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Nebivolol 5 mg exerts similar effects on time and frequency domain indexes of HRV as 50 mg atenolol. Nebivolol attenuates sympathetic tone, but does not appear to promote vagal activity more than atenolol.
Patients with IHD, class II-III angina and moderately severe compensated or subcompensated type II diabetes (n=35, 29 with grade 1-2 hypertension according to WHO 1999 classification) were divided into 2 groups with similar clinical and laboratory characteristics. Patients of group 1 received metoprolol (50-100 mg/day), of group 2--nebivolol (5-7.5 mg/day) for 8 weeks. Data of physical investigation, exercise tests, 24-hour blood pressure and heart rate monitoring, analysis of lipid spectrum and glycemic profile were used for assessment of treatment efficacy.
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Whereas classical beta-blockers do not affect cell growth, only nebivolol inhibits haCSMC or haEC proliferation and induces a moderate rate of apoptosis. Furthermore, in HaCEs NO formation increases and endothelin-1 secretion decreases suggesting that nebivolol may represent a beta-blocker with great promises in CAD therapy.
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Mirabegron markedly relaxed isolated CC strips by activating β3 -adrenoceptors independently of the NO-cGMP pathway. There is also evidence of the existence of a close functional link between β3 -adrenoceptors and the RhoA/ROCK pathway. These results may support further clinical studies using combinations of mirabegron with ROCK and phosphodiesterase type 5 inhibitors (PDE5i) for the treatment of ED, especially in patients who do not respond to PDE5i therapy.