Conditions: Prehypertension Hypertension
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 42
Healthy volunteers: yes

Brief summary:
The investigators hypothesize that nebivolol will reduce ET-1-mediated vasoconstrictor tone in adult humans with elevated blood pressure to a greater extent than either metoprolol or placebo.

Detailed description:
1. The investigators hypothesize that nebivolol will reduce ET-1-mediated vasoconstrictor tone in adult humans with elevated blood pressure to a greater extent than either metoprolol or placebo.
2. The investigators further hypothesize that reducing ET-1 vasoconstrictor activity contributes to the improvement in endothelial vasodilator function associated with nebivolol.

Arms:
arm 1: Systolic and Diastolic blood pressure will be measured before and after randomization to12 weeks of Nebivolol. Forearm blood flow will be measured in response to 100 nmol/min of BQ-123, BQ-123+BQ788 (50 mol/min), Acetylcholine (4.0, 8.0, 16.0 ug/100 mL tissue/min), Sodium Nitroprusside (1.0, 2.0, 4.0 ug/100 mL tissue/min) and BQ-123+BQ-788+Acetylcholine (same doses as above) will be measured before and after the 12 weeks of nebivolol. arm 2: Systolic and Diastolic blood pressure will be measured before and after randomization to12 weeks of Metoprolol. Forearm blood flow will be measured in response to 100 nmol/min of BQ-123, BQ-123+BQ788 (50 mol/min), Acetylcholine (4.0, 8.0, 16.0 ug/100 mL tissue/min), Sodium Nitroprusside (1.0, 2.0, 4.0 ug/100 mL tissue/min) and BQ-123+BQ-788+Acetylcholine (same doses as above) will be measured before and after the 12 weeks of Metoprolol. arm 3: Systolic and Diastolic blood pressure will be measured before and after randomization to12 weeks of placebo. Forearm blood flow will be measured in response to 100 nmol/min of BQ-123, BQ-123+BQ788 (50 mol/min), Acetylcholine (4.0, 8.0, 16.0 ug/100 mL tissue/min), Sodium Nitroprusside (1.0, 2.0, 4.0 ug/100 mL tissue/min) and BQ-123+BQ-788+Acetylcholine (same doses as above) will be measured before and after the 12 weeks of placebo.

Interventions: intervention 1: Nebivolol intervention 2: Metoprolol intervention 3: Placebo intervention 4: Forearm Blood Flow (FBF) response to BQ-123 (100 mol/min) intervention 5: FBF response to BQ-123 (100 nmol/min)+BQ-788(50 nmol/min) intervention 6: FBF response to Acetylcholine intervention 7: FBF response to Sodium Nitroprusside intervention 8: FBF response to BQ-123+BQ-788+ACh
Intervention descriptions: intervention 1: 5 mg tablet to be taken by mouth once per day for 12 weeks intervention 2: 100 mg tablet to be taken by mouth once per day for 12 weeks intervention 3: gelatin capsule to be taken by mouth once per day for 12 weeks intervention 4: The forearm blood flow response to the endothelin (ET) -1 A receptor blocker BQ-123 (100 nmol/min) for 60 minutes at baseline and at 12 weeks. intervention 5: The FBF response to the nonselective endothelin (ET) -1 receptor blockade BQ-123 (100 nmol/min) + BQ-788 (50 nmol/min)for 60 minutes at baseline and at 12 weeks. intervention 6: The FBF response to the endothelium-dependent vasodilator ACh (4, 8 and 16 ug/100 mL tissue/min) at baseline and at 12 weeks. intervention 7: The FBF response to the endothelium independent vasodilator NTP (1,2 and 4 ug/100 mL tissue/min) at baseline and at 12 weeks. intervention 8: The FBF response to the nonselective endothelin (ET) -1 receptor blockade BQ-123 (100 nmol/min) + BQ-788 (50 nmol/min)for 60 minutes at baseline and at 12 weeks.

Protocol document: