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

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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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All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Okamoto, L. E., Gamboa, A., Shibao, C. A., Arnold, A. C., Choi, L., Black, B. K., Raj, S. R., Robertson, D., & Biaggioni, I. (2014). Nebivolol, but not metoprolol, lowers blood pressure in nitric oxide-sensitive human hypertension. Hypertension, 64(6), 1241-1247. https://doi.org/10.1161/HYPERTENSIONAHA.114.04116