Article

Nebivolol Reverses Endothelial Dysfunction in Essential Hypertension A Randomized, Double-Blind, Crossover Study

Hypertension Research Centre, Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Dundee, United Kingdom.
Circulation (Impact Factor: 14.43). 08/2001; 104(5):511-4. DOI: 10.1161/hc3001.094207
Source: PubMed

ABSTRACT

Vascular endothelial dysfunction may predict future atherosclerosis. Hence, an antihypertensive agent that reverses endothelial dysfunction and lowers blood pressure might improve the prognosis of patients with hypertension. We hypothesized that nebivolol, a vasodilating beta-blocker, could improve endothelial dysfunction. We tested this hypothesis by comparing the effects of nebivolol and atenolol on endothelial function.
Twelve hypertensive patients with a mean ambulatory blood pressure of 154+/-7/97+/-10 mm Hg were randomized after a 2-week placebo run-in period (baseline) in a double-blind, crossover fashion to 8-week treatment periods with either 5 mg of nebivolol with 2.5 mg of bendrofluazide or 50 mg of atenolol with 2.5 mg of bendrofluazide. Forearm venous occlusion plethysmography and intra-arterial infusions of acetylcholine and N(G)-monomethyl-L-arginine (L-NMMA) were used to assess stimulated and basal endothelium-dependent nitric oxide release, respectively. Sodium nitroprusside was used as an endothelium-independent control. Nebivolol/bendrofluazide and atenolol/bendrofluazide each lowered the clinic blood pressure to the same extent (132+/-7/82+/-6 and 132+/-9/83+/-8 mm Hg, respectively; P<0.001 from baseline). The vasodilatory response to acetylcholine was significantly increased with nebivolol/bendrofluazide (maximum percentage change in forearm blood flow [mean+/-SEM], 435+/-27%, P<0.001) but not with atenolol/bendrofluazide. Similarly, the endothelium-dependent vasoconstrictive response to L-NMMA was significantly improved only with nebivolol treatment (percentage change in forearm blood flow, -54+/-5%; P<0.001). The response to sodium nitroprusside was not different between treatments, suggesting that the endothelium-independent pathway was unaffected.
Nebivolol/bendrofluazide increased both stimulated and basal endothelial nitric oxide release, whereas for the same degree of blood pressure control, atenolol/bendrofluazide had no effect on nitric oxide bioactivity. Thus, nebivolol may offer additional vascular protection in treating hypertension.

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Available from: Nikolaos Tzemos, Jan 24, 2014
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    • "Indeed, this drug is currently used in the treatment of arterial hypertension (McNeely and Goa, 1999) because it is characterized by its ability to lower the blood pressure attributed to its vasodilatory properties mediated by the L-arginine/NO pathway (Ritter, 2001; Ignarro et al., 2002; De Nigris et al., 2008a). All the recent studies have shown that nebivolol possesses endothelio-, nephro-and cardio-protective effects (Sorrentino et al., 2011; De Nigris et al., 2008b; Georgescu et al., 2005; Tzemos et al., 2001). Taken together, these studies lead to the hypothesis that nebivolol may also have beneficial effects on the genital system and fetal growth during pregnancy. "
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    ABSTRACT: The aim of study was to evaluate the effects of nebivolol, a cardioselective beta-1 adrenergic receptor blocker of the third generation with vasodilatory properties, vs. bisoprolol on the genital circulation, uterine vasculature, fetal growth and postnatal development in pregnant Wistar rats. Non invasive measurements of systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR), and invasive measurement of genital blood flow (GBF) were taken in pregnant rats, by tail cuff and transonic probe methods respectively, after an oral treatment by gastric gavage with nebivolol (8mg/kg/day) or bisoprolol (10mg/kg/day) from day 11 to day 18 of pregnancy. Other morphometrical and histological measurements were performed on the ovarian and uterine arteries to evaluate the effect of nebivolol on the uterine vasculature. Furthermore, postnatal mortality and pup growth were recorded. The data demonstrated that nebivolol (compared with bisoprolol) induced a significant decrease in SBP, HR and GBF while DBP remained unchanged. Moreover, nebivolol increased the diameter and the length of ovarian and uterine arteries and the number of uterine artery segmental branches. The results also showed that the body weight gain of newborns in the nebivolol group was significantly lower vs. bisoprolol and vs. control with a higher mortality rate. The nebivolol action is not only limited to its favorable hemodynamic effects represented by a decrease in blood pressure, but it also produces adverse effects on fetal growth and postnatal development that may limit its therapeutic use in females during pregnancy. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Apr 2015 · European journal of pharmacology
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    • "Indeed, this drug is currently used in the treatment of arterial hypertension (McNeely and Goa, 1999) because it is characterized by its ability to lower the blood pressure attributed to its vasodilatory properties mediated by the L-arginine/NO pathway (Ritter, 2001; Ignarro et al., 2002; De Nigris et al., 2008a). All the recent studies have shown that nebivolol possesses endothelio-, nephro-and cardio-protective effects (Sorrentino et al., 2011; De Nigris et al., 2008b; Georgescu et al., 2005; Tzemos et al., 2001). Taken together, these studies lead to the hypothesis that nebivolol may also have beneficial effects on the genital system and fetal growth during pregnancy. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of study was to evaluate the effects of nebivolol, a cardioselective beta-1 adrenergic receptor blocker of the third generation with vasodilatory properties, vs. bisoprolol on the genital circulation, uterine vasculature, fetal growth and postnatal development in pregnant Wistar rats. Non invasive measurements of systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR), and invasive measurement of genital blood flow (GBF) were taken in pregnant rats, by tail cuff and transonic probe methods respectively, after an oral treatment by gastric gavage with nebivolol (8 mg/kg/day) or bisoprolol (10 mg/kg/day) from day 11 to day 18 of pregnancy. Other morphometrical and histological measurements were performed on the ovarian and uterine arteries to evaluate the effect of nebivolol on the uterine vasculature. Furthermore, postnatal mortality and pup growth were recorded. The data demonstrated that nebivolol (compared with bisoprolol) induced a significant decrease in SBP, HR and GBF while DBP remained unchanged. Moreover, nebivolol increased the diameter and the length of ovarian and uterine arteries and the number of uterine artery segmental branches. The results also showed that the body weight gain of newborns in the nebivolol group was significantly lower vs. bisoprolol and vs. control with a higher mortality rate. The nebivolol action is not only limited to its favorable hemodynamic effects represented by a decrease in blood pressure, but it also produces adverse effects on fetal growth and postnatal development that may limit its therapeutic use in females during pregnancy. &
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    • "Nebivolol ist ein langwirkender β 1 ­selektiver Betarezeptorenblocker mit zusätzlichen vasodilatierenden Eigenschaften, die auf einer endothelabhängi­ gen NO­Freisetzung beruhen (Bowman et al. 1994, Moen und Wagstaff 2006). Die Freisetzung von NO trägt zur Verbesserung der endothelialen Dysfunktion bei (Tzemos et al. 2001). Nebivolol scheint die NO­Freisetzung unter Bindung an Östrogenrezeptoren mit konsekutiver Stimulation der endothelialen NO­ Synthase zu fördern (Grundt et al. 2007). "

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