The favorable kinetics and balance of nebivolol-stimulated nitric oxide and peroxynitrite release in human endothelial cells

Mason, R. Preston; Jacob, Robert F.; Corbalan, J. Jose; Szczesny, Damian; Matysiak, Kinga; Maliński, Tadeusz

doi:10.1186/2050-6511-14-48

Cited by 24 publications

(29 citation statements)

References 27 publications

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“…Nebivolol was also found to increase NO release in cultured endothelial cells and isolated arteries . The stimulatory effect of nebivolol may be mediated through β 2 ‐ or β 3 ‐receptors . Oral nebivolol in combination with bendroflumethiazide for 8 weeks increased both basal and stimulated endothelium‐derived NO estimated by forearm venous occlusion plethysmography and intra‐arterial infusions of acetylcholine and L‐NMMA .…”

Section: Discussionmentioning

confidence: 92%

“…In vitro incubation of isolated vessels and in vivo infusion in forearm vasculature with nebivolol was found to induce vasodilatation, which could be blocked by inhibition of NO synthesis . Nebivolol was also found to increase NO release in cultured endothelial cells and isolated arteries . The stimulatory effect of nebivolol may be mediated through β 2 ‐ or β 3 ‐receptors .…”

Section: Discussionmentioning

confidence: 96%

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Effect of nebivolol on renal nitric oxide availability and tubular function in patients with essential hypertension

Mose

Jensen

Therwani

et al. 2015

Brit J Clinical Pharma

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Aims Nebivolol is a selective β1‐receptor antagonist with vasodilating properties. In patients with essential hypertension, we tested the hypothesis that nebivolol increases systemic and renal nitric oxide (NO) availability using L‐NG‐monomethyl arginine (L‐NMMA) as an inhibitor of NO production. Methods In a randomized, placebo‐controlled, crossover study, patients with essential hypertension were treated with nebivolol for five days, along with a standardized diet and fluid intake. We examined the acute effects of systemic NO synthase inhibition with L‐NMMA on brachial blood pressure (bBP), pulse wave velocity (PWV) and central blood pressure (cBP) estimated by applanation tonometry, glomerular filtration rate (GFR), fractional excretion of sodium (FENa), urinary excretion of both aquaporin‐2 (u‐AQP2) and epithelial sodium channels (u‐ENaCγ), and plasma concentrations of nitrate/nitrite (p‐NOx) and vasoactive hormones after five days' treatment with placebo and nebivolol. Results Nebivolol significantly reduced PWV, bBP, cBP and plasma renin, angiotensin II and aldosterone concentrations. The renal parameters, p‐NOx and plasma arginine vasopressin concentration were not changed by nebivolol. There was no difference between nebivolol and placebo in the response to L‐NMMA, with LMMA inducing a similar increase in PWV, bBP and cBP and a similar decrease in GFR, uAQP2 and u‐ENaCγ and FENa [mean change −0.62% (95% confidence interval {CI} −0.40 to −0.84) during placebo vs. −0.57% (95% CI −0.46 to −0.68; P = 0.564) during nebivolol treatment]. Vasoactive hormones were changed to a similar extend by L‐NMMA during administration of nebivolol and placebo. Conclusions Nebivolol did not change p‐NOx, and inhibition of NO synthesis induced the same response in blood pressure, GFR, renal tubular function and vasoactive hormones during nebivolol and placebo. Thus, the data did not support the hypothesis that nebivolol changes vascular and renal NO availability in patients with essential hypertension.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 96%

Effect of nebivolol on renal nitric oxide availability and tubular function in patients with essential hypertension

Mose

Jensen

Therwani

et al. 2015

Brit J Clinical Pharma

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“…. The same group quantified PON after release upon stimulation by a beta-blocker medication, Nebivolol(135) as illustrated in inset (G).…”

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confidence: 98%

Meat Freshness: Peroxynitrite’s Oxidative Role, Its Natural Scavengers, and New Measuring Tools

Vasilescu

Vezeanu

Liu

et al. 2014

ACS Symposium Series

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Typically, about $1 billion/year is lost when red meat loses freshness on the shelf. Consumer purchasing decisions depend on meat color and flavor, which are strongly influenced by complex nitro-oxidative events within meat muscle tissue. One goal of this chapter is to explain the loss in meat freshness linked to the action of peroxynitrite anion ONOO-, a strong nitro-oxidative agent. The toxicity of abnormally high ONOOlevels in vivo has been proven, and ONOO -is also suspected of accelerating meat spoilage by two principal mechanisms:(1) oxidation of iron atoms in heme-containing globin proteins, leading to a color change from red to brown, and (2) peroxidation of unsaturated lipids, leading to flavor degradation. A second goal is to review electrochemical quantification methods for ONOO-and its oxidative effects on biologically relevant molecules, including unsaturated phospholipids within biological membranes and heme-containing molecules. A third goal is to examine the natural polyphenols that protect against peroxynitrite-induced oxidative damage. The final goal is to

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“…[2][3][4][5] It is a racemic mixture of D-and L-enantiomers, of which D-nebivolol is considered to be a highly selective b-adrenergic receptor antagonist. [5][6][7][8] It was demonstrated that nebivolol stimulates NO release through both b 3 -receptor and adenosine triphosphate-dependent, P2Y-receptor activation.…”

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confidence: 99%

“…[5][6][7][8] It was demonstrated that nebivolol stimulates NO release through both b 3 -receptor and adenosine triphosphate-dependent, P2Y-receptor activation. 3,[9][10][11][12] In a well-designed clinical study, Tzemos and coworkers 13 analyzed whether nebivolol could improve endothelial dysfunction in patients with essential hypertension. They showed that nebivolol/bendrofluazide increased both stimulated and basal endothelial NO release, whereas, for the same degree of blood pressure control, atenolol/bendrofluazide had no effect on NO bioactivity; therefore, they concluded that nebivolol may offer additional vascular protection in treating hypertension.…”

mentioning

confidence: 99%

Nebivolol and Endothelial Dysfunction in Patients With Essential Hypertension: A Reputation Saver of β‐Blockers?

Çelik

Öztürk

Balta

et al. 2016

J of Clinical Hypertension

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We have read with great interest the recently published article by Neuman and coworkers 1 in which they hypothesized that nebivolol, a selective b 1 -antagonist that stimulates nitric oxide (NO), improves endothelial function in African Americans with hypertension when compared with metoprolol. In that well-designed study, the authors found evidence for NO bioavailability at rest during treatment with both nebivolol and metoprolol succinate in hypertensive African American patients, with a clear trend for a greater contribution of NO during nebivolol therapy. Moreover, after combined blockade of NO and endothelium-derived hyperpolarizing factor (EDHF), there was significantly greater vasoconstriction during nebivolol compared with metoprolol therapy, suggesting a greater contribution of both NO and EDHF combined to resting vasomotor tone during nebivolol treatment. Moreover, the contribution of NO to exercise-induced vasodilation was greater during treatment with nebivolol compared with metoprolol succinate.Nebivolol is a third-generation, b 1 -adrenergic receptor antagonist that has vasodilatory properties both in animals and humans independent of b 1 -receptor antagonism and related to b 3 -receptor agonist effects. 2-5It is a racemic mixture of D-and L-enantiomers, of which D-nebivolol is considered to be a highly selective b-adrenergic receptor antagonist.5-8 It was demonstrated that nebivolol stimulates NO release through both b 3 -receptor and adenosine triphosphate-dependent, P2Y-receptor activation.3,9-12 In a well-designed clinical study, Tzemos and coworkers 13 analyzed whether nebivolol could improve endothelial dysfunction in patients with essential hypertension. They showed that nebivolol/bendrofluazide increased both stimulated and basal endothelial NO release, whereas, for the same degree of blood pressure control, atenolol/bendrofluazide had no effect on NO bioactivity; therefore, they concluded that nebivolol may offer additional vascular protection in treating hypertension. 13 Moreover, Oelze and coworkers 14 demonstrated that nebivolol but not metoprolol improved endothelial function and reduced vascular oxidative stress in an experimental model of AngII-induced hypertension. These effects were associated with a normalization of the expression of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits Nox1, Nox2, p22phox, p47phox, p67phox, and Rac1 and an inhibition of NOS III uncoupling in a rat hypertension model. More importantly, they found that nebivolol but not metoprolol inhibited activation of vascular NADPH oxidase and were able to dissociate an already assembled and active membrane-associated NADPH oxidase complex. These observations indicate that nebivolol, in addition to its b 1 -receptor-blocking and NO-releasing effects, possesses substantial inhibitory effects on vascular oxidative stress, all of which may beneficially influence endothelial dysfunction because of oxidative stress in the setting of arterial hypertension.14 It is well-known that essential hyperten...

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The favorable kinetics and balance of nebivolol-stimulated nitric oxide and peroxynitrite release in human endothelial cells

Cited by 24 publications

References 27 publications

Effect of nebivolol on renal nitric oxide availability and tubular function in patients with essential hypertension

Effect of nebivolol on renal nitric oxide availability and tubular function in patients with essential hypertension

Meat Freshness: Peroxynitrite’s Oxidative Role, Its Natural Scavengers, and New Measuring Tools

Nebivolol and Endothelial Dysfunction in Patients With Essential Hypertension: A Reputation Saver of β‐Blockers?

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