The Effects of Nebivolol on the NO-system in Patients With Essential Hypertension
Condition: Essential Hypertension
MeSH terms: Hypertension; Essential Hypertension
Study type: Interventional
Phase: Phase 2

Summary: 
      Investigators want investigate the following hypothesis:

        1. Nebivolol increases nitric oxide activity in the systemic circulation and the kidney

        2. The increased activity of nitric oxide during nebivolol treatment can be demonstrated by
           inhibition of NO synthesis with L-NMMA. We expect increased responses in blood pressure
           and sodium excretion is expected during nebivolol treatment compared to placebo.
    

Detailed description: 
      Beta-blockers are no longer recommended as first line treatment in essential hypertension.
      Evidence mainly based on clinical trails with the non-vasodilating beta-blockers atenolol and
      propanolol points towards that beta-blockers have an increased risk of stroke compared to
      ACE-inhibitors, calcium channel blockers and thiazides. However, this Nebivolol is a third
      generation beta-blocker with vasodilating properties. Nebivolol decreases peripheral blood
      pressure to the same extend as other beta-blockers but in contrast to atenolol nebivolol also
      reduces central blood pressure. Furthermore nebivolol increases nitric oxide (NO)
      availability in forearm vessels, maybe through activation of beta-3 receptors. The nitric
      oxide system plays a central role in both renal sodium and water handling and regulation of
      vascular tone and blood pressure. It has not been investigated if nebivolol changes NO
      availability in the kidney.

      Investigators want investigate the following hypothesis:

        1. Nebivolol increases nitric oxide activity in the systemic circulation and the kidney

        2. The increased activity of nitric oxide during nebivolol treatment can be demonstrated by
           inhibition of NO synthesis with L-NMMA. Investigators expect increased responses in
           blood pressure and sodium excretion is expected during nebivolol treatment compared to
           placebo.

      Purpose The purpose of this study is to investigate the effects of nebivolol on renal
      handling of sodium and water (Glomerular filtration rate, urine production, free water
      clearance, excretion of proteins from epithelial sodium channels (u-ENaCαβγ) and aquaporin
      channels (u-AQP2) and sodium and potassium excretion), plasma concentrations of vasoactive
      hormones (renin, angiotensin II, aldosterone, vasopressin, atrial natriuretic peptide, brain
      natriuretic peptide and endothelin), central blood pressure, pulse wave velocity (PWV) and
      augmentation index, under basal conditions and during inhibition of nitric oxide synthesis in
      patients with essential hypertension.

      Design 25 patients with essential hypertension are recruited in this randomised, cross over,
      placebo-controlled, double blinded study with two treatment periods (nebivolol/placebo). Each
      subject will attend to two examination days. Four days prior to each examination days and on
      the morning of each examination day subjects are given either nebivolol 5 mg pr. day or
      placebo. During treatment periods subject are given a standardized diet. On the examination
      days subject are given L-NMMA, a nitric oxide synthase inhibitor, and renal function, central
      hemodynamic and vasoactive hormones are evaluated during basal conditions and during
      inhibition of nitric oxide synthesis.

      Perspectives This study is expected to contribute to increasing the knowledge about the
      mechanisms involved in the development and progression of cardiovascular disease.
      Beta-blockers are not recommended as first line treatment in essential hypertension but the
      results from this study may influence clinical treatment of essential hypertension in the
      future.
    

Intervention name(s): Nebivolol; placebo
Intervention type(s): Drug; Drug
Intervention description(s): Tablet i blinded in capsula
Other intervention name(s): Tradename in Denmark: Hypoloc
Intervention MeSH terms: Nebivolol
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Essential hypertension; Nitric oxide; Nebivolol; Fractional excretion of sodium