The Experts below are selected from a list of 2367 Experts worldwide ranked by ideXlab platform
Robert S Reneman - One of the best experts on this subject based on the ideXlab platform.
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Nebivolol a third generation beta blocker that augments vascular nitric oxide release endothelial beta 2 adrenergic receptor mediated nitric oxide production
Circulation, 2000Co-Authors: Martijn A W Broeders, Pieter A Doevendans, B C A M Bekkers, R J P Bronsaer, E Van Gorsel, Johan W M Heemskerk, Mirjam Oude G A Egbrink, E Van Breda, Robert S Reneman, R Van Der ZeeAbstract:Background—Nebivolol is a β1-selective adrenergic receptor antagonist with proposed nitric oxide (NO)–mediated vasodilating properties in humans. In this study, we explored whether Nebivolol indeed induces NO production and, if so, by what mechanism. We hypothesized that not Nebivolol itself but rather its metabolites augment NO production. Methods and Results—Mouse thoracic aorta segments were bathed in an organ chamber. Administration of Nebivolol did not affect NO production. When Nebivolol was allowed to metabolize in vivo in mice, addition of plasma of these mice caused a sustained 2-fold increase in NO release. Interestingly, coadministration of a selective β2-adrenergic receptor antagonist (butoxamine) prevented the response. Immunohistochemistry and Western blot analysis demonstrated the presence of β2- but not β1-adrenergic receptors on endothelial cells. In the absence of calcium, metabolized Nebivolol failed to increase NO production, suggesting a role for calcium-dependent NO synthase. With di...
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Nebivolol a third generation β blocker that augments vascular nitric oxide release endothelial β2 adrenergic receptor mediated nitric oxide production
Circulation, 2000Co-Authors: Martijn A W Broeders, Pieter A Doevendans, B C A M Bekkers, R J P Bronsaer, Johan W M Heemskerk, Mirjam Oude G A Egbrink, E Van Gorsel, E Van Breda, Robert S RenemanAbstract:Background—Nebivolol is a β1-selective adrenergic receptor antagonist with proposed nitric oxide (NO)–mediated vasodilating properties in humans. In this study, we explored whether Nebivolol indeed induces NO production and, if so, by what mechanism. We hypothesized that not Nebivolol itself but rather its metabolites augment NO production. Methods and Results—Mouse thoracic aorta segments were bathed in an organ chamber. Administration of Nebivolol did not affect NO production. When Nebivolol was allowed to metabolize in vivo in mice, addition of plasma of these mice caused a sustained 2-fold increase in NO release. Interestingly, coadministration of a selective β2-adrenergic receptor antagonist (butoxamine) prevented the response. Immunohistochemistry and Western blot analysis demonstrated the presence of β2- but not β1-adrenergic receptors on endothelial cells. In the absence of calcium, metabolized Nebivolol failed to increase NO production, suggesting a role for calcium-dependent NO synthase. With di...
Michael Bohm - One of the best experts on this subject based on the ideXlab platform.
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effects of the long term administration of Nebivolol on the clinical symptoms exercise capacity and left ventricular function of patients with diastolic dysfunction results of the elandd study
European Journal of Heart Failure, 2012Co-Authors: Viviane M Conraads, Marco Metra, Michael Bohm, Otto Kamp, Gilles W De Keulenaer, Burkert Pieske, Jose Zamorano, Panos E Vardas, Livio Dei CasAbstract:Aims We hypothesized that Nebivolol, a beta-blocker with nitric oxide-releasing properties, could favourably affect exercise capacity in patients with heart failure and preserved left ventricular ejection fraction (HFPEF). Methods and results A total of 116 subjects with HFPEF, in New York Heart Association (NYHA) functional class II–III, with left ventricular ejection fraction (LVEF) >45%, and with echo-Doppler signs of LV diastolic dysfunction, were randomized to 6 months treatment with Nebivolol or placebo, following a double-blind, parallel group design. The primary endpoint of the study was the change in 6 min walk test distance (6MWTD) after 6 months. Nebivolol did not improve 6MWTD (from 420 ±143 to 428 ±141 m with Nebivolol vs. from 412 ±123 to 446 ±119 m with placebo, P = 0.004 for interaction) compared with placebo, and the peak oxygen uptake also remained unchanged (peakVO2; from 17.02 ±4.79 to 16.32 ±3.76 mL/kg/min with Nebivolol vs. from 17.79 ±5.96 to 18.59 ±5.64 mL/kg/min with placebo, P = 0.63 for interaction). Resting and peak blood pressure and heart rate decreased with Nebivolol. A significant correlation was found between the change in peak exercise heart rate and that in peakVO2 (r = 0.391; P = 0.003) for the Nebivolol group. Quality of life, assessed using the Minnesota Living with Heart Failure™ Questionnaire, and NYHA classification improved to a similar extent in both groups, whereas N-terminal pro brain natriuretic peptide (NT-pro BNP) plasma levels remained unchanged. Conclusions Compared with placebo, 6 months treatment with Nebivolol did not improve exercise capacity in patients with HFPEF. Its negative chronotropic effect may have contributed to this result.
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efficacy and safety of Nebivolol in elderly heart failure patients with impaired renal function insights from the seniors trial
European Journal of Heart Failure, 2009Co-Authors: Alain Cohensolal, Dipak Kotecha, Dirk J Van Veldhuisen, Daphne Babalis, Michael Bohm, Andrew J S Coats, Michael Roughton, Philip A Poolewilson, Luigi Tavazzi, Marcus FlatherAbstract:Aim To determine the safety and efficacy of Nebivolol in elderly heart failure (HF) patients with renal dysfunction. Methods and results SENIORS recruited patients aged 70 years or older with symptomatic HF, irrespective of ejection fraction, and randomized them to Nebivolol or placebo. Patients (n = 2112) were divided by tertile of estimated glomerular filtration rate (eGFR). Mean age of patients was 76.1 years, 35% of patients had an ejection fraction of >35%, and 37% were women resulting in a unique cohort, far more representative of clinical practice than previous trials. eGFR was strongly associated with outcomes and Nebivolol was similarly efficacious across eGFR tertiles. The primary outcome rate (all-cause mortality or cardiovascular hospital admission) and adjusted hazard ratio for Nebivolol use in those with low eGFR was 40% and 0.84 (95% CI 0.67–1.07), 31% and 0.79 (0.60–1.04) in the middle tertile, and 29% and 0.86 (0.65–1.14) in the highest eGFR tertile. There was no interaction noted between renal function and the treatment effect (P = 0.442). Nebivolol use in patients with moderate renal impairment (eGFR <60) was not associated with major safety concerns, apart from higher rates of drug-discontinuation due to bradycardia. Conclusion Nebivolol is safe and has a similar effect in elderly HF patients with mild or moderate renal impairment.
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beta blockade with Nebivolol in elderly heart failure patients with impaired and preserved left ventricular ejection fraction data from seniors study of effects of Nebivolol intervention on outcomes and rehospitalization in seniors with heart failure
Journal of the American College of Cardiology, 2009Co-Authors: Dirk J Van Veldhuisen, Alain Cohensolal, Daphne Babalis, Michael Bohm, Andrew J S Coats, Michael Roughton, Philip A Poolewilson, Marcus Flather, Stefan D Anker, Seniors InvestigatorsAbstract:Objectives In this pre-specified subanalysis of the SENIORS (Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors With Heart Failure) trial, which examined the effects of Nebivolol in elderly heart failure (HF) patients, we explored the effects of left ventricular ejection fraction (EF) on outcomes, including the subgroups impaired EF (≤35%) and preserved EF (>35%). Background Beta-blockers are established drugs in patients with HF and impaired EF, but their value in preserved EF is unclear. Methods We studied 2,111 patients; 1,359 (64%) had impaired (≤35%) EF (mean 28.7%) and 752 (36%) had preserved (>35%) EF (mean 49.2%). The effect of Nebivolol was investigated in these 2 groups, and it was compared to explore the interaction of EF with outcome. Follow-up was 21 months; the primary end point was all-cause mortality or cardiovascular hospitalizations. Results Patients with preserved EF were more often women (49.9% vs. 29.8%) and had less advanced HF, more hypertension, and fewer prior myocardial infarctions (all p Conclusions The effect of beta-blockade with Nebivolol in elderly patients with HF in this study was similar in those with preserved and impaired EF.
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Nebivolol but not metoprolol improves endothelial function of the corpus cavernosum in apolipoprotein e knockout mice
Journal of Pharmacology and Experimental Therapeutics, 2008Co-Authors: Magnus Baumhakel, N Schlimmer, Kansu Buyukafsar, Onur Arikan, Michael BohmAbstract:To determine the effects and underlying mechanisms of treatment with the β-receptor blockers Nebivolol and metoprolol on penile endothelial function in apolipoprotein E (ApoE)-/- mice, wild-type (WT) and ApoE-/- mice were fed with a cholesterol-rich diet for 7 weeks. ApoE-/- mice were treated with Nebivolol (10 mg/kg/day) or metoprolol (90 mg/kg/day). Endothelial function of aortic and corpora cavernosal tissue was assessed by pharmacological stimulation with carbachol (endothelium dependent) or glycerol trinitrate (endothelium independent) in organ bath experiments. Atherosclerotic lesion formation was evaluated with oil-red staining, and modulation of reactive oxygen species (ROS) production was determined with lipid peroxidation. Heart rate, but not blood pressure, was decreased in Nebivolol- and metoprolol-treated ApoE-/- mice ( p < 0.01) compared with controls and WT mice without significant intergroup differences. Atherosclerotic lesion formation in the aortic root was increased in ApoE-/- mice ( p < 0.01) with a more significant improvement in Nebivolol- ( p < 0.01) compared with metoprolol-treated mice ( p < 0.05). Endothelium-dependent relaxation of the corpora cavernosa was significantly impaired in ApoE-/- mice ( p < 0.05), which improved in Nebivolol- versus metoprolol-treated mice. Efficacy of endothelium-dependent relaxation was comparable in aortic and penile tissue. Quantification of ROS production via lipid peroxidation revealed a significant reduction of superoxide anion production in Nebivolol-treated ( p < 0.05) but not metoprolol-treated mice compared with ApoE-/- controls. Nebivolol improves penile endothelial function as a surrogate of erectile function in ApoE-/- mice. These effects may be related to a reduction of ROS production, which is independent of heart rate reduction, because metoprolol did not increase endothelial function.
Martijn A W Broeders - One of the best experts on this subject based on the ideXlab platform.
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Nebivolol a third generation beta blocker that augments vascular nitric oxide release endothelial beta 2 adrenergic receptor mediated nitric oxide production
Circulation, 2000Co-Authors: Martijn A W Broeders, Pieter A Doevendans, B C A M Bekkers, R J P Bronsaer, E Van Gorsel, Johan W M Heemskerk, Mirjam Oude G A Egbrink, E Van Breda, Robert S Reneman, R Van Der ZeeAbstract:Background—Nebivolol is a β1-selective adrenergic receptor antagonist with proposed nitric oxide (NO)–mediated vasodilating properties in humans. In this study, we explored whether Nebivolol indeed induces NO production and, if so, by what mechanism. We hypothesized that not Nebivolol itself but rather its metabolites augment NO production. Methods and Results—Mouse thoracic aorta segments were bathed in an organ chamber. Administration of Nebivolol did not affect NO production. When Nebivolol was allowed to metabolize in vivo in mice, addition of plasma of these mice caused a sustained 2-fold increase in NO release. Interestingly, coadministration of a selective β2-adrenergic receptor antagonist (butoxamine) prevented the response. Immunohistochemistry and Western blot analysis demonstrated the presence of β2- but not β1-adrenergic receptors on endothelial cells. In the absence of calcium, metabolized Nebivolol failed to increase NO production, suggesting a role for calcium-dependent NO synthase. With di...
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Nebivolol a third generation β blocker that augments vascular nitric oxide release endothelial β2 adrenergic receptor mediated nitric oxide production
Circulation, 2000Co-Authors: Martijn A W Broeders, Pieter A Doevendans, B C A M Bekkers, R J P Bronsaer, Johan W M Heemskerk, Mirjam Oude G A Egbrink, E Van Gorsel, E Van Breda, Robert S RenemanAbstract:Background—Nebivolol is a β1-selective adrenergic receptor antagonist with proposed nitric oxide (NO)–mediated vasodilating properties in humans. In this study, we explored whether Nebivolol indeed induces NO production and, if so, by what mechanism. We hypothesized that not Nebivolol itself but rather its metabolites augment NO production. Methods and Results—Mouse thoracic aorta segments were bathed in an organ chamber. Administration of Nebivolol did not affect NO production. When Nebivolol was allowed to metabolize in vivo in mice, addition of plasma of these mice caused a sustained 2-fold increase in NO release. Interestingly, coadministration of a selective β2-adrenergic receptor antagonist (butoxamine) prevented the response. Immunohistochemistry and Western blot analysis demonstrated the presence of β2- but not β1-adrenergic receptors on endothelial cells. In the absence of calcium, metabolized Nebivolol failed to increase NO production, suggesting a role for calcium-dependent NO synthase. With di...
Jose M Cuezva - One of the best experts on this subject based on the ideXlab platform.
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coordinate β adrenergic inhibition of mitochondrial activity and angiogenesis arrest tumor growth
Nature Communications, 2020Co-Authors: Cristina Nuevotapioles, Fulvio Santacatterina, Konstantinos Stamatakis, Cristina Nunez De Arenas, Marta Gomez De Cedron, Laura Formentini, Jose M CuezvaAbstract:Mitochondrial metabolism has emerged as a promising target against the mechanisms of tumor growth. Herein, we have screened an FDA-approved library to identify drugs that inhibit mitochondrial respiration. The β1-blocker Nebivolol specifically hinders oxidative phosphorylation in cancer cells by concertedly inhibiting Complex I and ATP synthase activities. Complex I inhibition is mediated by interfering the phosphorylation of NDUFS7. Inhibition of the ATP synthase is exerted by the overexpression and binding of the ATPase Inhibitory Factor 1 (IF1) to the enzyme. Remarkably, Nebivolol also arrests tumor angiogenesis by arresting endothelial cell proliferation. Altogether, targeting mitochondria and angiogenesis triggers a metabolic and oxidative stress crisis that restricts the growth of colon and breast carcinomas. Nebivolol holds great promise to be repurposed for the treatment of cancer patients. Targeting mitochondrial metabolism in cancer cells has shown promising therapeutic potential. Here, the authors screen FDA-approved compound library and show that the β1-blocker Nebivolol inhibits oxidative phosphorylation and angiogenesis in cancer cells and can be re-purposed for cancer therapy.
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coordinate β adrenergic inhibition of mitochondrial activity and angiogenesis arrest tumor growth
Nature Communications, 2020Co-Authors: Cristina Nuevotapioles, Fulvio Santacatterina, Konstantinos Stamatakis, Cristina Nunez De Arenas, Marta Gomez De Cedron, Laura Formentini, Jose M CuezvaAbstract:Mitochondrial metabolism has emerged as a promising target against the mechanisms of tumor growth. Herein, we have screened an FDA-approved library to identify drugs that inhibit mitochondrial respiration. The β1-blocker Nebivolol specifically hinders oxidative phosphorylation in cancer cells by concertedly inhibiting Complex I and ATP synthase activities. Complex I inhibition is mediated by interfering the phosphorylation of NDUFS7. Inhibition of the ATP synthase is exerted by the overexpression and binding of the ATPase Inhibitory Factor 1 (IF1) to the enzyme. Remarkably, Nebivolol also arrests tumor angiogenesis by arresting endothelial cell proliferation. Altogether, targeting mitochondria and angiogenesis triggers a metabolic and oxidative stress crisis that restricts the growth of colon and breast carcinomas. Nebivolol holds great promise to be repurposed for the treatment of cancer patients.
Marcus Flather - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of Nebivolol in elderly heart failure patients with impaired renal function insights from the seniors trial
European Journal of Heart Failure, 2009Co-Authors: Alain Cohensolal, Dipak Kotecha, Dirk J Van Veldhuisen, Daphne Babalis, Michael Bohm, Andrew J S Coats, Michael Roughton, Philip A Poolewilson, Luigi Tavazzi, Marcus FlatherAbstract:Aim To determine the safety and efficacy of Nebivolol in elderly heart failure (HF) patients with renal dysfunction. Methods and results SENIORS recruited patients aged 70 years or older with symptomatic HF, irrespective of ejection fraction, and randomized them to Nebivolol or placebo. Patients (n = 2112) were divided by tertile of estimated glomerular filtration rate (eGFR). Mean age of patients was 76.1 years, 35% of patients had an ejection fraction of >35%, and 37% were women resulting in a unique cohort, far more representative of clinical practice than previous trials. eGFR was strongly associated with outcomes and Nebivolol was similarly efficacious across eGFR tertiles. The primary outcome rate (all-cause mortality or cardiovascular hospital admission) and adjusted hazard ratio for Nebivolol use in those with low eGFR was 40% and 0.84 (95% CI 0.67–1.07), 31% and 0.79 (0.60–1.04) in the middle tertile, and 29% and 0.86 (0.65–1.14) in the highest eGFR tertile. There was no interaction noted between renal function and the treatment effect (P = 0.442). Nebivolol use in patients with moderate renal impairment (eGFR <60) was not associated with major safety concerns, apart from higher rates of drug-discontinuation due to bradycardia. Conclusion Nebivolol is safe and has a similar effect in elderly HF patients with mild or moderate renal impairment.
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beta blockade with Nebivolol in elderly heart failure patients with impaired and preserved left ventricular ejection fraction data from seniors study of effects of Nebivolol intervention on outcomes and rehospitalization in seniors with heart failure
Journal of the American College of Cardiology, 2009Co-Authors: Dirk J Van Veldhuisen, Alain Cohensolal, Daphne Babalis, Michael Bohm, Andrew J S Coats, Michael Roughton, Philip A Poolewilson, Marcus Flather, Stefan D Anker, Seniors InvestigatorsAbstract:Objectives In this pre-specified subanalysis of the SENIORS (Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors With Heart Failure) trial, which examined the effects of Nebivolol in elderly heart failure (HF) patients, we explored the effects of left ventricular ejection fraction (EF) on outcomes, including the subgroups impaired EF (≤35%) and preserved EF (>35%). Background Beta-blockers are established drugs in patients with HF and impaired EF, but their value in preserved EF is unclear. Methods We studied 2,111 patients; 1,359 (64%) had impaired (≤35%) EF (mean 28.7%) and 752 (36%) had preserved (>35%) EF (mean 49.2%). The effect of Nebivolol was investigated in these 2 groups, and it was compared to explore the interaction of EF with outcome. Follow-up was 21 months; the primary end point was all-cause mortality or cardiovascular hospitalizations. Results Patients with preserved EF were more often women (49.9% vs. 29.8%) and had less advanced HF, more hypertension, and fewer prior myocardial infarctions (all p Conclusions The effect of beta-blockade with Nebivolol in elderly patients with HF in this study was similar in those with preserved and impaired EF.
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randomized trial to determine the effect of Nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure seniors
European Heart Journal, 2005Co-Authors: Marcus Flather, Alain Cohensolal, Dirk J Van Veldhuisen, Andrew J S Coats, Marcelo C Shibata, Aleksandr Parkhomenko, Joszef Borbola, Dan Dumitrascu, Roberto Ferrari, Philippe LechatAbstract:Aims Large randomized trials have shown that beta-blockers reduce mortality and hospital admissions in patients with heart failure. The effects of beta-blockers in elderly patients with a broad range of left ventricular ejection fraction are uncertain. The SENIORS study was performed to assess effects of the beta-blocker, Nebivolol, in patients ≥70 years, regardless of ejection fraction. Methods and results We randomly assigned 2128 patients aged ≥70 years with a history of heart failure (hospital admission for heart failure within the previous year or known ejection fraction ≤35%), 1067 to Nebivolol (titrated from 1.25 mg once daily to 10 mg once daily), and 1061 to placebo. The primary outcome was a composite of all cause mortality or cardiovascular hospital admission (time to first event). Analysis was by intention to treat. Mean duration of follow-up was 21 months. Mean age was 76 years (SD 4.7), 37% were female, mean ejection fraction was 36% (with 35% having ejection fraction >35%), and 68% had a prior history of coronary heart disease. The mean maintenance dose of Nebivolol was 7.7 mg and of placebo 8.5 mg. The primary outcome occurred in 332 patients (31.1%) on Nebivolol compared with 375 (35.3%) on placebo [hazard ratio (HR) 0.86, 95% CI 0.74–0.99; P =0.039]. There was no significant influence of age, gender, or ejection fraction on the effect of Nebivolol on the primary outcome. Death (all causes) occurred in 169 (15.8%) on Nebivolol and 192 (18.1%) on placebo (HR 0.88, 95% CI 0.71–1.08; P =0.21). Conclusion Nebivolol, a beta-blocker with vasodilating properties, is an effective and well-tolerated treatment for heart failure in the elderly.
