Effects of Nebivolol on Skeletal Muscle During Exercise in Hypertensive Patients
Condition: Hypertension
MeSH terms: Hypertension
Intervention: Metoprolol succinate; Nebivolol; Non-invasive measurement of Cardiac Output (CO); Endothelial cell collection; Microvascular perfusion assessment using Definity
Intervention description: The subject will be started on metoprolol succinate (Toprol XL) 100-300mg daily, which he or she will continue for a period of 12 weeks. Following the 12-week treatment period, the procedures listed below will be performed. After completion of the study procedures, the medication will be discontinued.; The subject will be started on nebivolol (Bystolic) 5-20mg daily, which he or she will continue for a period of 12 weeks. Following the 12-week treatment period, the procedures listed below will be performed. After completion of the study procedures, the medication will be discontinued.; Cardiac Output (CO) will be measured non-invasively at rest and during exercise by thoracic electrical bioimpedance. Stroke volume will be derived from change in impedance/time measured during electrical systole. Cardiac output will be determined as the product of stroke volume and heart rate.; We will collect endothelial cells from a superficial vein, usually in the arm. Following insertion of a peripheral intravenous (IV) catheter, we will collect cells from the inner lining of the vein using a thin, flexible J-tipped wire. The wire will be inserted through the IV into the vein and then removed, along with a sampling of endothelial cells. The cells collected will be processed and stained for several proteins involved in endothelial cell function, using immunofluorescent technique.; Using high-resolution ultrasound, we will measure skeletal muscle blood flow during infusion of a solution containing the octafluoropropane microbubble contrast agent, Definity. The solution will be a dilution of 1 vial of Definity to 30 cc of normal saline. The ultrasound probe will be placed over the forearm to obtain images while octafluoropropane microbubbles (Definity) are infused intravenously at the rate of 0.20 to 0.27 ml/min, not to exceed a maximum dose of 2 vials per study subject per day or visit. The microvascular perfusion assessment using Definity be performed at rest as well as during slow and fast handgrip exercises.
Intervention MeSH terms: Metoprolol; Nebivolol
Phase: Phase 4
Study type: Interventional
Primary purpose: Diagnostic
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: hypertension; blood pressure; blood pressure medications; metoprolol; nebivolol; vascular oxidative stress; nitric oxide; nitric oxide synthase (eNOS); endothelium; endothelial dysfunction; endothelial cell protein expression; microvascular blood flow; flow mediated dilation; handgrip exercise; endothelial cell collection; microbubbles; Definity

Summary:

      The purpose of this study is to determine if Nebivolol improves microvascular perfusion in
      skeletal muscle during exercise in hypertensive patients and whether this improvement is
      accompanied by reduction in vascular oxidative stress or increased endothelial nitric oxide
      synthase (eNOS) expression in humans.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men and women with stage I primary untreated hypertension (BP between 140-159/90-99
             mmHg)

          -  Age 18-65

        Exclusion Criteria:

          -  Congestive heart failure

          -  Coronary artery disease

          -  Left ventricular hypertrophy by echocardiography or ECG

          -  History of stroke

          -  Average blood pressure >159/99 mmHg

          -  Bradycardia with a resting heart rate <55 bpm

          -  Chronic kidney disease with a serum creatinine > 1.4 mg/dL

          -  Asthma or chronic obstructive pulmonary disease

          -  Women who are pregnant or planning to become pregnant

          -  Hypersensitivity to beta blockers, hydrochlorothiazide, or Definity

          -  Any history of substance abuse (other than tobacco)

          -  Concomitant drug treatment which raises endogenous nitric oxide levels, including
             nitrates or phosphodiesterase V inhibitors (Viagra, Levitra)

          -  History of symptomatic bradycardia or heart block

          -  Patients with Right-to-left, bidirectional, or transient right-to-left cardiac shunts

          -  Hypersensitivity to perflutren, blood, blood products or albumin.