Renal Sympathetic Denervation Suppresses de novo Podocyte Injury and Albuminuria in Rats with Aortic Regurgitation
Background—The presence of chronic kidney disease is a significant independent risk factor for poor prognosis in patients with chronic heart failure (CHF). However, the mechanisms and mediators underlying this interaction are poorly understood. In this study, we tested our hypothesis that chronic cardiac volume overload leads to de novo renal dysfunction by co-activating the sympathetic nervous system (SNS) and the renin-angiotensin system (RAS) in the kidney. We also examined the therapeutic potential of renal denervation and RAS inhibition to suppress renal injury in CHF.
Methods and Results—Sprague-Dawley rats underwent aortic regurgitation (AR) and were treated for 6 months with either vehicle, olmesartan [an angiotensin II (AngII) receptor blocker], or hydralazine. At 6 months, albuminuria and glomerular podocyte injury were significantly increased in AR rats. These changes were associated with increased urinary angiotensinogen excretion, kidney AngII and norepinephrine (NE) levels, as well as enhanced angiotensinogen and angiotensin type 1a receptor gene expression, and oxidative stress in renal cortical tissues. AR rats with renal denervation had decreased albuminuria and glomerular podocyte injury, which were associated with reduced kidney NE, angiotensinogen, AngII and oxidative stress. Renal denervation combined with olmesartan prevented podocyte injury and albuminuria induced by AR.
Conclusions—In this chronic cardiac volume overload animal model, activation of the SNS augments kidney RAS and oxidative stress, which act as crucial cardio-renal mediators. Renal denervation and olmesartan prevent the onset and progression of renal injury, providing new insight into the treatment of cardio-renal syndrome.
- aortic regurgitation
- cardio-renal syndrome
- renin angiotensin system
- sympathetic nervous system
- Received August 23, 2011.
- Accepted February 3, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited