Nebivolol Treatment Reduces Serum Levels of Asymmetric Dimethylarginine and Improves Endothelial Dysfunction in Essential Hypertensive Patients

Pasini, Anna Fratta; Garbin, Ulisse; Stranieri, Chiara; Boccioletti, Veronica; Mozzini, Chiara; Manfro, Stefania; Pasini, Andrea; Cominacini, Mattia; Cominacini, Luciano

doi:10.1038/ajh.2008.260

Cited by 80 publications

(62 citation statements)

References 41 publications

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“…The endothelial effects of nebivolol are unique amongst beta-blockers and have been replicated in other studies. 121,122 Recent work by Vitale et al has suggested that nebivolol in combination with hydrochlorthiazide might at least be non-inferior to irbesartan with hydrochlorthiazide, perhaps giving some hope to beta-blockers in hypertension. 123 Indeed, a recent meta-analysis of 1,273 patients from 16 studies by Peller et al on the effects of beta-blockers on endothelial function in various groups of patients did shown some benefit, however the study did include somewhat homogenous groups of patients.…”

Section: Diuretics and Beta-blockersmentioning

confidence: 99%

Endothelial dysfunction in human essential hypertension

Mordi

Delles

et al. 2016

Journal of Hypertension

123

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Abstract:Although the endothelium has a number of important functions, the term endothelial dysfunction is commonly used to describe impairment in its vasodilatory capacity. It is increasingly recognised that this is related to hypertension, although whether it predates hypertension or is a consequence of it is still unknown. In this review we explore the mechanisms of endothelial dysfunction in hypertension, its prognostic significance and methods of pharmacological reversal. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation CONDENSED ABSTRACTEndothelial dysfunction is prevalent in hypertension and has a recognised association with the condition. In this article we review the pathophysiology of endothelial dysfunction in human hypertension, its prognostic significance and methods of pharmacological reversal. We appreciate the opportunity to revise this manuscript again and particularly would like to thank Reviewer whose constructive criticism has certainly improved the manuscript. We have addressed the minor comments suggested as attached to this letter.We are extremely grateful once again to the reviewers and the editors for their detailed critique which has undoubtedly improved the quality of the manuscript.We thank you once again for the opportunity to resubmit our manuscript and look forward to your decision. Yours sincerely Dr Ify Mordi Submission letterReviewer #2:I thank you the author for their last revision: the paper improved quite a lot! Just few points should be still addressed:We thank the reviewer for their positive appraisal of our revised manuscript -we agree that the comments provided have substantially improved the review. We agree with the reviewer that this sentence is out of place. Given the length of the review and the fact that this is covered elsewhere we have now deleted the sentence.-Please move the description of micromyography to the invasive methods as tissue biopsies are necessary.We thank the reviewer for pointing out this error. We have now moved the description of myography to the invasive methods section (page 5). We have no conflict of interest. Endothelial Dysfunction in Human Essential Hypertension Manuscript 2 ABSTRACTAlthough the endothelium has a number of important functions, the term endothelial

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Section: Diuretics and Beta-blockersmentioning

confidence: 99%

Endothelial dysfunction in human essential hypertension

Mordi

Delles

et al. 2016

Journal of Hypertension

123

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“…To evaluate the previously reported effect of ␤-AR blocker treatment on endogenous nitric oxide (NO) synthase (NOS) inhibitor ADMA in hypertensive patients, we determined circulating ADMA before and after treatment (21). To determine whether nebivolol attenuates impair microvascular flow during exercise by increased EC expression p47 phox NADPH oxidase subunit resulting in increased oxidative stress, we performed peripheral venous EC collection in the same subjects (n ϭ 25) as previously described (6).…”

Section: Experimental Protocolsmentioning

confidence: 99%

Differential effects of nebivolol vs. metoprolol on microvascular function in hypertensive humans

Velasco

Solow

Price

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Use of ␤-adrenergic receptor (AR) blocker is associated with increased risk of fatigue and exercise intolerance. Nebivolol is a newer generation ␤-blocker, which is thought to avoid this side effect via its vasodilating property. However, the effects of nebivolol on skeletal muscle perfusion during exercise have not been determined in hypertensive patients. Accordingly, we performed contrast-enhanced ultrasound perfusion imaging of the forearm muscles in 25 untreated stage I hypertensive patients at rest and during handgrip exercise at baseline or after 12 wk of treatment with nebivolol (5-20 mg/day) or metoprolol succinate (100 -300 mg/day), with a subsequent double crossover for 12 wk. Metoprolol and nebivolol each induced a reduction in the resting blood pressure and heart rate (130.9 Ϯ 2.6/81.7 Ϯ 1.8 vs. 131.6 Ϯ 2.7/80.8 Ϯ 1.5 mmHg and 63 Ϯ 2 vs. 64 Ϯ 2 beats/min) compared with baseline (142.1 Ϯ 2.0/88.7 Ϯ 1.4 mmHg and 75 Ϯ 2 beats/min, respectively, both P Ͻ 0.01). Metoprolol significantly attenuated the increase in microvascular blood volume (MBV) during handgrip at 12 and 20 repetitions/min by 50% compared with baseline (mixed-model P Ͻ 0.05), which was not observed with nebivolol. Neither metoprolol nor nebivolol affected microvascular flow velocity (MFV). Similarly, metoprolol and nebivolol had no effect on the increase in the conduit brachial artery flow as determined by duplex Doppler ultrasound. Thus our study demonstrated a first direct evidence for metoprolol-induced impairment in the recruitment of microvascular units during exercise in hypertensive humans, which was avoided by nebivolol. This selective reduction in MBV without alteration in MFV by metoprolol suggested impaired vasodilation at the precapillary arteriolar level.exercise; sympathetic nervous system; muscle blood flow; hypertension NEW & NOTEWORTHYWe identified a deleterious effect of chronic administration of metoprolol on microvascular function during handgrip in hypertensive patients, which was not observed with nebivolol. The impaired muscle capillary recruitment during exercise may predispose to development of exercise intolerance.PREVIOUS STUDIES DEMONSTRATED impaired muscle capillary recruitment in hypertension (8, 12), possibly related to impaired microvascular function or capillary rarefaction (27,28). In hypertensive patients, both metoprolol and propranolol can further impair microvascular function by acutely reducing resting capillary blood flow in the skeletal muscle (22, 23), which may predispose to development of exercise intolerance or fatigue. Nebivolol is a third-generation ␤-adrenergic receptor (AR) blocker that also possesses vasodilator properties (35). The vasodilator effect is attributed to partly due to the antioxidant effect via inhibition of NADPH oxidase activity or reduced expression of the NADPH oxidase subunits p47 phox (18,20, 35). However, the chronic effect of either older or newer generation ␤-AR blockers on microvascular function during exercise and endothelial cell (EC) expression of the p47 phox N...

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“…In 14 out of 15 studies, the ischemia lasted for 5 min, in 1 study it was 4.5 min [9]. In 12 studies, the cuff was placed on the forearm and in 3 studies measurements was performed with cuff placed on the arm [10][11][12]. Six studies reported the number of observers who assessed FMD [9,10,[13][14][15][16].…”

Section: Fmd Measurementsmentioning

confidence: 99%