Evidence map›Paper›PMID 25267802›Full record

Trial reportHypertension (Dallas, Tex. : 1979)2014

Nebivolol, but not metoprolol, lowers blood pressure in nitric oxide-sensitive human hypertension.

Luis E Okamoto, Alfredo Gamboa, Cyndya A Shibao, Amy C Arnold, Leena Choi, Bonnie K Black, Satish R Raj, David Robertson, Italo Biaggioni

Registry-linked trialOpen access · bronzeAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Hypertension (Dallas, Tex. : 1979), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03847350 (An Observational Study to Identify BEnefits After 24 Weeks of NEBILET®), which is not on this map. Cited by 20 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 3 pooled it
3.4field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03847350 completednot on this mapstarted 2015, after this paper: background citation

An Observational Study to Identify BEnefits After 24 Weeks of NEBILET®(Nebivolol) Administration For Essential hypertensIon Patients With Various Co-morbidities and Treatment Environments in KOREA.

TypeobservationalSponsorA.Menarini Asia-Pacific Holdings Pte LtdRan2015 to 2017Enrolled3,250ConditionsEssential Hypertension
3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 3 syntheses or guidelines pooled it, 51 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Supine blood pressure measurement and its emerging role in cardiovascular risk stratification.Hypertension research : official journal of the Japanese Society of Hypertension · 2026
    Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Review
  12. Review
  13. Pharmacologic treatment of orthostatic hypotension.Autonomic neuroscience : basic & clinical · 2020
    Review
  14. Treatment of autonomic dysfunction in Parkinson disease and other synucleinopathies.Movement disorders : official journal of the Movement Disorder Society · 2018
    Review
  15. Review
  16. Review
  17. Anti-VEGF-Induced Hypertension: a Review of Pathophysiology and Treatment Options.Current treatment options in cardiovascular medicine · 2016
    Article
  18. Review
  19. Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Luis E OkamotoFrom the Vanderbilt Autonomic Dysfunction Center and Division of Clinical Pharmacology, Department of Medicine (L.E.O., A.G., C.A.S., A.C.A., B.K.B., S.R.R., D.R., I.B.), and Departments of Pharmacology (S.R.R., D.R., I.B.), Neurology (D.R.), and Biostatistics (L.C.), Vanderbilt University School of Medicine, Nashville, TN.
Alfredo GamboaFrom the Vanderbilt Autonomic Dysfunction Center and Division of Clinical Pharmacology, Department of Medicine (L.E.O., A.G., C.A.S., A.C.A., B.K.B., S.R.R., D.R., I.B.), and Departments of Pharmacology (S.R.R., D.R., I.B.), Neurology (D.R.), and Biostatistics (L.C.), Vanderbilt University School of Medicine, Nashville, TN.
Cyndya A ShibaoFrom the Vanderbilt Autonomic Dysfunction Center and Division of Clinical Pharmacology, Department of Medicine (L.E.O., A.G., C.A.S., A.C.A., B.K.B., S.R.R., D.R., I.B.), and Departments of Pharmacology (S.R.R., D.R., I.B.), Neurology (D.R.), and Biostatistics (L.C.), Vanderbilt University School of Medicine, Nashville, TN.
Amy C ArnoldFrom the Vanderbilt Autonomic Dysfunction Center and Division of Clinical Pharmacology, Department of Medicine (L.E.O., A.G., C.A.S., A.C.A., B.K.B., S.R.R., D.R., I.B.), and Departments of Pharmacology (S.R.R., D.R., I.B.), Neurology (D.R.), and Biostatistics (L.C.), Vanderbilt University School of Medicine, Nashville, TN.
Leena ChoiFrom the Vanderbilt Autonomic Dysfunction Center and Division of Clinical Pharmacology, Department of Medicine (L.E.O., A.G., C.A.S., A.C.A., B.K.B., S.R.R., D.R., I.B.), and Departments of Pharmacology (S.R.R., D.R., I.B.), Neurology (D.R.), and Biostatistics (L.C.), Vanderbilt University School of Medicine, Nashville, TN.
Bonnie K BlackFrom the Vanderbilt Autonomic Dysfunction Center and Division of Clinical Pharmacology, Department of Medicine (L.E.O., A.G., C.A.S., A.C.A., B.K.B., S.R.R., D.R., I.B.), and Departments of Pharmacology (S.R.R., D.R., I.B.), Neurology (D.R.), and Biostatistics (L.C.), Vanderbilt University School of Medicine, Nashville, TN.
Satish R RajFrom the Vanderbilt Autonomic Dysfunction Center and Division of Clinical Pharmacology, Department of Medicine (L.E.O., A.G., C.A.S., A.C.A., B.K.B., S.R.R., D.R., I.B.), and Departments of Pharmacology (S.R.R., D.R., I.B.), Neurology (D.R.), and Biostatistics (L.C.), Vanderbilt University School of Medicine, Nashville, TN.
David RobertsonFrom the Vanderbilt Autonomic Dysfunction Center and Division of Clinical Pharmacology, Department of Medicine (L.E.O., A.G., C.A.S., A.C.A., B.K.B., S.R.R., D.R., I.B.), and Departments of Pharmacology (S.R.R., D.R., I.B.), Neurology (D.R.), and Biostatistics (L.C.), Vanderbilt University School of Medicine, Nashville, TN.
Italo BiaggioniFrom the Vanderbilt Autonomic Dysfunction Center and Division of Clinical Pharmacology, Department of Medicine (L.E.O., A.G., C.A.S., A.C.A., B.K.B., S.R.R., D.R., I.B.), and Departments of Pharmacology (S.R.R., D.R., I.B.), Neurology (D.R.), and Biostatistics (L.C.), Vanderbilt University School of Medicine, Nashville, TN. Italo.biaggioni@vanderbilt.edu.
Vanderbilt University · US

Funding

VANDERBILT UNIVERSITY CTSA FOR PEDIATRIC RESEARCHUL1RR024975 · NCRR · VANDERBILT UNIVERSITY · PI BERNARD, GORDON RAPHAEL · 2007 to 2011
$45.7M
The Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4M
Structural genomics of norepinephrine transportersP01HL056693 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ROBERTSON, DAVID HERLIE · 1997 to 2016
$30.8M
CLINICAL PHARMACOLOGY TRAINING PROGRAMT32GM007569 · NIGMS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Bjorn C Knollmann · 1985 to 2026
$12.4M
Training CoreU54NS065736 · NINDS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI FREEMAN, ROY · 2009 to 2018
$11.6M
Autonomic Nervous System in Chronic Fatigue SyndromeR01NS055670 · NINDS · VANDERBILT UNIVERSITY · PI BIAGGIONI, ITALO · 2006 to 2009
$1.5M
Sympathetic Nervous System and Nitric Oxide in Obesity Associated HypertensionK23HL095905 · NHLBI · VANDERBILT UNIVERSITY · PI GAMBOA, ALFREDO · 2010 to 2014
$754k
NCATS NIH HHS 2 UL1 TR000445-06NCATS NIH HHS UL1 TR000445NCRR NIH HHS UL1 RR024975NCRR NIH HHS UL1 RR024975-01NHLBI NIH HHS P01 HL056693NHLBI NIH HHS P01 HL56693NIGMS NIH HHS T32 GM007569NINDS NIH HHS R01 NS055670NINDS NIH HHS U54 NS065736
6 · The paper itself

Abstract

Nebivolol, unlike other selective β1-receptor blockers, induces vasodilation attributable to increased NO bioavailability. The relative contribution of this mechanism to the blood pressure (BP)-lowering effects of nebivolol is unclear because it is normally masked by baroreflex buffering. Autonomic failure provides a unique model of hypertension devoid of autonomic modulation but sensitive to the hypotensive effects of NO potentiation. We tested the hypothesis that nebivolol would decrease BP in these patients through a mechanism independent of β-blockade. We randomized 20 autonomic failure patients with supine hypertension (14 men; 69±2 years) to receive a single oral dose of placebo, nebivolol 5 mg, metoprolol 50 mg (negative control), and sildenafil 25 mg (positive control) on separate nights in a double-blind, crossover study. Supine BP was monitored every 2 hours from 8:00 pm to 8:00 am. Compared with placebo, sildenafil and nebivolol decreased systolic BP during the night (P<0.001 and P=0.036, by mixed-effects model, maximal systolic BP reduction 8-hour postdrug of -20±6 and -24±9 mm Hg, respectively), whereas metoprolol had no effect. In a subanalysis, we divided patients into sildenafil responders (BP fall>20 mm Hg at 4:00 am) and nonresponders. Nebivolol significantly lowered systolic BP in sildenafil responders (-44±13 mm Hg) but not in nonresponders (1±11 mm Hg). Despite lowering nighttime BP, nebivolol did not worsen morning orthostatic tolerance compared with placebo. In conclusion, nebivolol effectively lowered supine hypertension in autonomic failure, independent of β1-blockade. These results are consistent with the hypothesis that NO potentiation contributes significantly to the antihypertensive effect of nebivolol.

Indexed as

Adrenergic beta-1 Receptor AntagonistsAgedBenzopyransBlood PressureCross-Over StudiesDose-Response Relationship, DrugDouble-Blind MethodEthanolaminesFemaleFollow-Up StudiesHumansHypertensionMaleMetoprololNebivololNitric OxideAdrenergic beta-1 Receptor AntagonistsBenzopyransEthanolaminesMetoprololNebivololNitric Oxideautonomic nervous systemhypertensionnebivololnitric oxide

Identifiers

PMID25267802
PMCPMC4230998
OpenAlexW2014594848

What OpenQuestion holds

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Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.