Original Report: Laboratory Investigation

Nebivolol Reduces Proteinuria and Renal NADPH Oxidase-Generated Reactive Oxygen Species in the Transgenic Ren2 Rat
Adam Whaley-Connell^{a, b, d}, Javad Habibi^{a, b, d}, Megan Johnson^{a, b}, Roger Tilmon^{a, b}, Nathan Rehmer^{a, b}, Jenna Rehmer^{a, b}, Charles Wiedmeyer^c, Carlos M. Ferrario^e, James R. Sowers<sup>a, b, d

a</sup>The University of Missouri School of Medicine,
^bDiabetes and Cardiovascular Center,
^cCollege of Veterinary Medicine,
^dThe Harry S. Truman VA Medical Center, Columbia, Mo., and
^eHypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, N.C., USA

Address of Corresponding Author

Am J Nephrol 2009;30:354-360 (DOI: 10.1159/000229305)

  Key Words

• Nebivolol
• Proteinuria
• NADPH oxidase
• Reactive oxygen species

  Abstract

Background/Aims: Renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system activation are crucial in the pathogenesis of hypertension, cardiovascular and renal disease. NADPH oxidase-mediated increases in reactive oxygen species (ROS) are an important mediator for RAAS-induced cardiovascular and renal injury. Increased levels of ROS can diminish the bioactivity of nitric oxide (NO), a critical modulator of RAAS effects on the kidney. Thereby, we hypothesized that in vivo nebivolol therapy in a rodent model of activated RAAS would attenuate glomerular damage and proteinuria through its actions to reduce NADPH oxidase activity/ROS and increase bioavailable NO. Methods: We utilized the transgenic Ren2 rat which displays heightened tissue RAAS, hypertension, and proteinuria. Ren2 rats (6-9 weeks of age) and age-matched Sprague-Dawley littermates were treated with nebivolol 10 mg/kg/day (osmotic mini-pump) for 21 days. Results: Ren2 rats exhibited increases in systolic blood pressure, proteinuria, kidney cortical tissue total NADPH oxidase activity and subunits (Rac1, p67^phox, and p47^phox), ROS and 3-nitrotyrosine, as well as reductions in podocyte protein markers; each of these parameters improved with nebivolol treatment along with increases in renal endothelial NO synthase expression. Conclusions: Our data suggest that nebivolol improves proteinuria through reductions in renal RAAS-mediated increases in NADPH oxidase/ROS and increases in bioavailable NO.

Copyright © 2009 S. Karger AG, Basel

  Author Contacts

Adam Whaley-Connell
University of Missouri-Columbia School of Medicine
Department of Internal Medicine, Division of Nephrology and Hypertension
CE417, DC043.0, Five, Hospital Dr., Columbia, MO 65212 (USA)
Tel. +1 573 882 7992, Fax +1 573 884 4820, E-Mail whaleyconnella@health.missouri.edu

  Article Information

Received: May 13, 2009
Accepted: June 15, 2009
Published online: July 17, 2009
Number of Print Pages : 7
Number of Figures : 4, Number of Tables : 0, Number of References : 30