Abstract 18718: Differential Effects of Nebivolol and Metoprolol on Oxidative Stress Markers and Circulating Progenitor Cells
Background: Unlike traditional beta-blockers, nebivolol activates nitric oxide (NO) release via partial agonist activity at beta-2/3 receptors. We hypothesized that this property of nebivolol compared to metoprolol would improve oxidative stress (OS) and mobilize progenitor cells (PCs) that are known to be enhanced by NO, and ultimately contribute to improved vascular health.
Methods: Thirty-two hypertensive subjects (age 54±10 years, 57% male, 83% African American) were randomized in a double-blind, cross-over study to receive either nebivolol or metoprolol for 3 months each. Of the 32 subjects randomized, 30 subjects successfully completed the trial. Two subjects did not complete the study due to serious adverse events. Nebivolol was titrated from 5mg to 20mg daily (mean 12mg) and metoprolol XL from 50mg to 200mg daily (mean 123mg). All other hypertensive therapy was kept constant. Measurements were made at baseline and on each drug after 3 and 6 months. OS was estimated from plasma levels of glutathione that reflects increased oxidative stress at lower levels. Circulating PCs were measured using flow cytometry for CD34+ and CD34+/CD133+ positive cells in mononuclear cell pools (CD45med). Arterial stiffness was measured as pulse wave velocity and augmentation index using the Sphygmacor device.
Results: Compared to baseline, both nebivolol and metoprolol significantly and equally lowered systolic and diastolic BP (p<0.01). Nebivolol, but not metoprolol significantly increased the glutathione level (from 1.08 to 1.50μM; p=0.04). Both nebivolol and metoprolol significantly increased circulating numbers of CD34+/CD133+ PCs compared to baseline by 28% and 18%, respectively (p=0.02, for both). Neither nebivolol nor metoprolol significantly changed indices of arterial stiffness.
Conclusion: Beta adrenergic antagonists increase circulating levels of PCs indicating improved regenerative capacity. Nebivolol, but not metoprolol, reduces oxidative stress, measured as plasma glutathione. The lack of translation of these effects on arterial stiffness may be secondary to the short duration of therapy in a treated population.
- © 2013 by American Heart Association, Inc.