title: Effect of nebivolol on renal nitric oxide availability and tubular function in patients with essential hypertension.
abstract: OBJECTIVE
  Nebivolol is a selective β1 -receptor antagonist with vasodilating properties. In patients with essential hypertension, we tested the hypothesis that nebivolol increases 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, along 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 excretion of both aquaporin-2 (u-AQP2) and epithelial sodium channels (u-ENaCγ ), and plasma concentrations of nitrate/nitrite (p-NOx ) and vasoactive hormones after five days' treatment with placebo and nebivolol.
  
  
  RESULTS
  Nebivolol significantly reduced PWV, bBP, cBP and plasma renin, angiotensin II and aldosterone concentrations. The renal parameters, p-NOx and plasma arginine vasopressin concentration were not changed by nebivolol. There was no difference between nebivolol and placebo in the response to L-NMMA, with LMMA inducing a similar increase in PWV, bBP and cBP and a similar decrease in GFR, uAQP2 and u-ENaCγ and FENa [mean change -0.62% (95% confidence interval {CI} -0.40 to -0.84) during placebo vs. -0.57% (95% CI -0.46 to -0.68; P = 0.564) during nebivolol treatment]. Vasoactive hormones were changed to a similar extend by L-NMMA during administration of nebivolol and placebo.
  
  
  CONCLUSIONS
  Nebivolol did not change p-NOx , and inhibition of NO synthesis induced the same response in blood pressure, GFR, renal tubular function and vasoactive hormones during nebivolol and placebo. Thus, the data did not support the hypothesis that nebivolol changes vascular and renal NO availability in patients with essential hypertension.
authors.affiliation: University Clinic in Nephrology and Hypertension, Department of Medical Research and University of Aarhus.
authors.forename: Frank H
authors.initials: FH
authors.lastname: Mose
authors.affiliation: University Clinic in Nephrology and Hypertension, Department of Medical Research and University of Aarhus.
authors.forename: Janni M
authors.initials: JM
authors.lastname: Jensen
authors.affiliation: University Clinic in Nephrology and Hypertension, Department of Medical Research and University of Aarhus.
authors.forename: Safa
authors.initials: S
authors.lastname: Therwani
authors.affiliation: Department of Nuclear Medicine.
authors.forename: Jesper
authors.initials: J
authors.lastname: Mortensen
authors.affiliation: Department of Clinical Biochemistry, Holstebro Hospital, Holstebro, Denmark.
authors.forename: Annebirthe B
authors.initials: AB
authors.lastname: Hansen
authors.affiliation: University Clinic in Nephrology and Hypertension, Department of Medical Research and University of Aarhus.
authors.forename: Jesper N
authors.initials: JN
authors.lastname: Bech
authors.affiliation: University Clinic in Nephrology and Hypertension, Department of Medical Research and University of Aarhus.
authors.forename: Erling B
authors.initials: EB
authors.lastname: Pedersen
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D000068577:Nebivolol / Q000008:administration & dosage / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D016896:Treatment Outcome; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D000068577:Nebivolol; D019323:omega-N-Methylarginine; D009569:Nitric Oxide
keywords: arterial stiffness; blood pressure; essential hypertension; fractional excretion of sodium; nebivolol; nitric oxide