Nebivolol and the Endothelin (ET)-1 System
Condition: Prehypertension; Hypertension
MeSH terms: Prehypertension
Intervention: Nebivolol; Metoprolol; Placebo; Forearm Blood Flow (FBF) response to BQ-123 (100 mol/min); FBF response to BQ-123 (100 nmol/min)+BQ-788(50 nmol/min); FBF response to Acetylcholine; FBF response to Sodium Nitroprusside; FBF response to BQ-123+BQ-788+ACh
Intervention description: 5 mg tablet to be taken by mouth once per day for 12 weeks; 100 mg tablet to be taken by mouth once per day for 12 weeks; gelatin capsule to be taken by mouth once per day for 12 weeks; 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.; 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.; The FBF response to the endothelium-dependent vasodilator ACh (4, 8 and 16 ug/100 mL tissue/min) at baseline and at 12 weeks.; The FBF response to the endothelium independent vasodilator NTP (1,2 and 4 ug/100 mL tissue/min) at baseline and at 12 weeks.; 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 MeSH terms: Metoprolol; Nebivolol; Nitroprusside; cyclo(Trp-Asp-Pro-Val-Leu); BQ 788; Acetylcholine
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 42.0
Sex: All
Minimum age: 45 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects will be men and women of all races and ethnic backgrounds aged 45-65 years.

          -  Subjects will be prehypertensive/hypertensive defined as resting systolic blood
             pressure >130 mmHg and < 160 mm Hg and/or diastolic blood pressure >80 mmHg and < 100
             mm Hg.

          -  All of the women in the study will be postmenopausal (at least 1 year from last
             menstrual cycle) and not receiving hormone replacement therapy (HRT) currently or in
             the preceding 3-year period.

          -  Lastly, candidates will be sedentary as determined from the Stanford Physical Activity
             Questionnaire (<35 kcal/wk) and will not have engaged in any program of regular
             physical activity for at least 1 year prior to the study.

        Exclusion Criteria:

          -  Candidates who smoke (currently or in the past 7 years), report more than low-risk
             alcohol consumption as defined as no more than 14 standard drinks/wk and no more than
             4 standard drinks/day for men and 7 standard drinks/wk and 3 standard drinks/day for
             women (a standard drink is defined as 12 ounces of beer, 5 ounces of wine, 1½ ounces
             of 80-proof distilled spirits)

          -  Potential candidates who are taking cardiovascular-acting (i.e. statins, blood
             pressure medication an aspirin) medications will not be eligible.

          -  Fasting plasma glucose >126 mg/dL.

          -  Potential candidates with a resting heart rate of < 50 beats/minute will be excluded.

          -  Use of hormone replacement therapy.

          -  In hypertensive subjects, a seated systolic blood pressure greater than 160 mmHg or a
             seated diastolic blood pressure greater than 100 mmHg.