Effect of nebivolol on renal NO availability and tubular function in patients with essential hypertension

Frank Holden Mose, Janni Majgaard Jensen, Safa Therwani, Jesper Mortensen, Annebirthe Bo Hansen, Jesper Nørgaard Bech, Erling Bjerregaard Pedersen

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Abstract

BACKGROUND: Nebivolol is a selective β1 -receptorantagonist with vasodilating properties. In patients with essential hypertension, we tested the hypothesis that nebivolol increased systemic and renal nitric oxide (NO) availability using L-N(G) -monomethyl arginine (L-NMMA) as an inhibitor of NO production.

METHODS: In a randomized, placebo-controlled, crossover study patients with essential hypertension were treated with nebivolol for five days with a standardized diet and fluid intake. We examined the acute effects of systemic NO synthase inhibition with L-NMMA on brachial blood pressure (bBP), pulse wave velocity (PWV) and central blood pressure (cBP) estimated by applanation tonometry, glomerular filtration rate (GFR), fractional excretion of sodium (FENa ), urinary excretions of aquaporin-2 (u-AQP2) and epithelial sodium channels (u-ENaCγ ) and plasma concentrations of nitrate/nitrite (p-NOx ) and vasoactive hormones after 5 day treatment with placebo and nebivolol.

RESULTS: Nebivolol significantly reduced PWV, bBP, cBP and PRC, p-AngII and p-Aldo. Renal parameters, p-NOx and p-AVP were not changed by nebivolol. During placebo and nebivolol, L-NMMA similarly increased PWV, bBP and cBP and similarly reduced GFR, uAQP2 and u-ENaCγ and FENa (-0.62% (-0.40;-0.84) during placebo vs. -0.57% (-0.46;-0.68) during nebivolol, mean with 95% CI, p = 0.564). Vasoactive hormones were changed to a similar extend by L-NMMA during nebivolol and placebo.

CONCLUSION: Nebivolol did not change p-NOx and inhibition of NO synthesis induced the same response in BP, GFR, renal tubular function and vasoactive hormones during nebivolol and placebo. Thus, the data does not support that nebivolol changes vascular and renal NO availability in patients with essential hypertension.

OriginalsprogEngelsk
TidsskriftBritish Journal of Clinical Pharmacology
Vol/bind80
Nummer3
Sider (fra-til)425-435
Antal sider11
ISSN0306-5251
DOI
StatusUdgivet - sep. 2015

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