The Effect of Nebivolol on Endothelial Dysfunction in African Americans With Hypertension
Condition: High Blood Pressure
MeSH terms: Hypertension
Intervention: Nebivolol; Metoprolol XL
Intervention description: Subjects will be randomized to either nebivolol or metoprolol xl, and remain on the study drug for 10 weeks. They will then "cross over" to take 10 weeks of the comparator drug.; Subjects will be randomized to either nebivolol or metoprolol xl, and remain on the study drug for 10 weeks. They will then "cross over" to take 10 weeks of the comparator drug.
Intervention MeSH terms: Metoprolol; Nebivolol
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 91.0
Sex: All
Minimum age: 21 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Nitric Oxide; Adrenergic beta-Antagonists; Antihypertensive Agents; Vasodilator Agents; Anti-Arrhythmia Agents; Sympatholytics; Vascular Resistance; Neurotransmitter Agents; Cardiovascular Diseases; Metoprolol succinate; Therapeutic Uses; Metoprolol; Vascular Diseases; Nebivolol; Cardiovascular Agents; Endothelium-Dependent Relaxing Factors

Summary:

      High blood pressure (hypertension) is called the "silent killer" because many people do not
      know they have it, and do not know when it is well controlled. Unfortunately, over time
      uncontrolled hypertension can cause irreversible organ damage that can lead to heart attack,
      stroke, heart failure, and kidney failure. If a person cannot control their blood pressure
      with diet and exercise, doctors often prescribe medications to help control the blood
      pressure. Nebivolol is a medication that has been recently approved by the FDA for the
      treatment of hypertension. Our study will investigate whether treatment with nebivolol, as
      compared to another medication called metoprolol, in African Americans with hypertension will
      be more effective in protecting blood vessels against the harmful effects of high blood
      pressure.

      Over time high blood pressure causes hardening of the arteries (atherosclerosis) which leads
      to narrowing of the blood vessels and reduces blood flow to our organs. Arteries also relax
      and contract naturally, which further changes the blood supply. When arteries are narrowed,
      exercise can bring on a condition in which the blood supply is inadequate, and this might
      result in the sensation of pain.

      Cells lining our blood vessels produce a variety of substances that normally cause arteries
      to relax. Two of these substances are called nitric oxide (NO) and endothelium-derived
      hyperpolarizing factor (EDHF). We are trying to determine the nature of these substances in
      African Americans with high blood pressure and how it is affected by nebivolol and
      metoprolol. One way to determine this is to inject drugs such as L-NMMA
      (N(G)-monomethyl-L-arginine) or TEA (tetraethylammonium chloride), which block the production
      of NO and EDHF respectively, and then study what happens to the blood flow at rest and during
      exercise. It is our thought that nebivolol, in comparison to metoprolol, will increase the
      substances that naturally cause arteries to relax and improve blood supply.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or post-menopausal females aged 18-80 years.

          -  Subjects self-identified as black or African-American.

          -  Diagnosis of hypertension.

          -  Patients on current anti-hypertensive therapy that does not include beta blockade
             should have BP >135/85.

          -  Patients on anti-hypertensive therapy including beta blockers will have their beta
             blockers discontinued gradually over 2 weeks before enrolment.

          -  Concomitant therapy: Patients will be allowed to be on concomitant therapy with
             aspirin, statins, thiazide diuretics, calcium antagonists (for treatment of
             hypertension), clonidine, or vasodilators. Patients will be on stable medical therapy
             for at least 2 months before recruitment. Patients with previous treatment with beta
             adrenergic blockers (metoprolol, propranolol, atenolol, and labetalol) will also be
             eligible to participate, but will be randomized to the study beta blocker.

        Exclusion Criteria:

          -  Initiation or change in dose of statin or other anti-hypertensive therapy within 2
             months before the study

          -  Inability to return to Emory for follow-up testing

          -  Age < 21 or >80 years

          -  Premenopausal females with potential for pregnancy

          -  Acute infection in previous 2 weeks

          -  On angiotensin antagonists (ACE inhibitors or ARBs)

          -  History of substance abuse

          -  Current neoplasm

          -  Chronic renal failure [creatinine > 2.5 mg/dL] or liver failure (liver enzymes >2X
             normal)

          -  Acute coronary syndrome, Class IV heart failure, CVA, coronary intervention within 2
             months

          -  Known aortic stenosis, hypertrophic cardiomyopathy.

          -  Inability to give informed consent