Nebivolol and Endothelial Regulation of Fibrinolysis (NERF)
Condition: Prehypertension; Hypertension
MeSH terms: Prehypertension
Intervention: Nebivolol; Metoprolol; Placebo; Bradykinin; Saline; Vitamin C
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; Bradykinin is infused into the brachial artery at doses of 12.5, 25.0 and 50.0 ng/100 mL of forearm tissue /min. BDK stimulates the endothelial cells to release tissue type plasminogen activator (t-PA). Blood flow in mL/100 mL tissue/min is also measured to BDK.; Baseline or resting forearm blood flow is measured in response to saline for 5 minutes before each drug infusion. t-PA release in response to the saline is also measured.; The acute effects of into-arterial vitamin C on the ability of the endothelium to release t-PA was determined before and after the nebivolol and metoprolol intervention. After allowing sufficient time (~20 minutes) for FBF and plasma t-PA concentrations to return to baseline following the initial infusion of BDK, vitamin C (24 mg/min) was infused at a constant rate while the BDK dose-response curves were repeated. t-PA and FBF were measured.
Intervention MeSH terms: Metoprolol; Nebivolol; Bradykinin; Kininogens
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 44.0
Sex: All
Minimum age: 45 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The investigators hypothesize that nebivolol will improve endothelial t-PA release in adult
      humans with elevated blood pressure to a greater extent than either metoprolol or placebo.
      The investigators further hypothesize that the improvement in the capacity of the vascular
      endothelium to release t-PA with nebivolol is mediated, in part, by the compound's
      antioxidant properties.
    

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 >125 mmHg and <160 mmHg and/or diastolic >80 mmHg and <100 mmHg.

          -  All of the women in the study will be postmenopausal and not receiving hormone
             replacement therapy (HRT) currently or in the preceding 3-year period.

          -  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 and 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 >160 mmHg or a seated
             diastolic blood pressure >100 mmHg will be excluded.