Nebivolol and Endothelial Regulation of Fibrinolysis (NERF)

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.

Conditions

• Prehypertension
• Hypertension

Interventions

DRUG

Nebivolol

5 mg tablet to be taken by mouth once per day for 12 weeks

DRUG

Metoprolol

100 mg tablet to be taken by mouth once per day for 12 weeks

DRUG

Placebo

Gelatin capsule to be taken by mouth once per day for 12 weeks

OTHER

Bradykinin

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.

OTHER

Saline

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.

OTHER

Vitamin C

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.

Sponsors & Collaborators

• Forest Laboratories

  collaborator INDUSTRY

• University of Colorado, Boulder

  lead OTHER

Principal Investigators

• Christopher DeSouza, Ph.D. · University of Colorado at Boulder

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

45 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2012-02-29

Primary Completion

2017-10-31

Completion

2017-10-31

Countries

• United States

Study Locations