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

Research output: Contribution to journalArticle

20 Citations (Scopus)

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, sildenafl 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.

Original languageEnglish (US)
Pages (from-to)1241-1247
Number of pages7
JournalHypertension
Volume64
Issue number6
DOIs
StatePublished - Jan 1 2014

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Nebivolol
Metoprolol
Nitric Oxide
Blood Pressure
Hypertension
Placebos
Baroreflex

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Okamoto, Luis E. ; Gamboa, Alfredo ; Shibao, Cyndya A. ; Arnold, Amy C. ; Choi, Leena ; Black, Bonnie K. ; Raj, Satish R. ; Robertson, David ; Biaggioni, Italo. / Nebivolol, but not metoprolol, lowers blood pressure in nitric oxide-sensitive human hypertension. In: Hypertension. 2014 ; Vol. 64, No. 6. pp. 1241-1247.
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title = "Nebivolol, but not metoprolol, lowers blood pressure in nitric oxide-sensitive human hypertension",
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, sildenafl 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.",
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Okamoto, LE, Gamboa, A, Shibao, CA, Arnold, AC, Choi, L, Black, BK, Raj, SR, Robertson, D & Biaggioni, I 2014, 'Nebivolol, but not metoprolol, lowers blood pressure in nitric oxide-sensitive human hypertension', Hypertension, vol. 64, no. 6, pp. 1241-1247. https://doi.org/10.1161/HYPERTENSIONAHA.114.04116

Nebivolol, but not metoprolol, lowers blood pressure in nitric oxide-sensitive human hypertension. / Okamoto, Luis E.; Gamboa, Alfredo; Shibao, Cyndya A.; Arnold, Amy C.; Choi, Leena; Black, Bonnie K.; Raj, Satish R.; Robertson, David; Biaggioni, Italo.

In: Hypertension, Vol. 64, No. 6, 01.01.2014, p. 1241-1247.

Research output: Contribution to journalArticle

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T1 - Nebivolol, but not metoprolol, lowers blood pressure in nitric oxide-sensitive human hypertension

AU - Okamoto, Luis E.

AU - Gamboa, Alfredo

AU - Shibao, Cyndya A.

AU - Arnold, Amy C.

AU - Choi, Leena

AU - Black, Bonnie K.

AU - Raj, Satish R.

AU - Robertson, David

AU - Biaggioni, Italo

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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, sildenafl 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.

AB - 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, sildenafl 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.

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