The Effect of Nebivolol on Endothelial Dysfunction in African Americans With Hypertension

The Effect of Nebivolol on Endothelial Dysfunction in African Americans With Hypertension

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.

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