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Circulation. 2012 Mar 20;125(11):1402-13. doi: 10.1161/CIRCULATIONAHA.111.064097. Epub 2012 Feb 10.

Renal sympathetic denervation suppresses de novo podocyte injury and albuminuria in rats with aortic regurgitation.

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Department of Cardiorenal and Cerebrovascular Medicine Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, Japan.



The presence of chronic kidney disease is a significant independent risk factor for poor prognosis in patients with chronic heart failure. 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 coactivating the sympathetic nervous system and renin-angiotensin system in the kidney. We also examined the therapeutic potential of renal denervation and renin-angiotensin system inhibition to suppress renal injury in chronic heart failure.


Sprague-Dawley rats underwent aortic regurgitation and were treated for 6 months with vehicle, olmesartan (an angiotensin II receptor blocker), or hydralazine. At 6 months, albuminuria and glomerular podocyte injury were significantly increased in aortic regurgitation rats. These changes were associated with increased urinary angiotensinogen excretion, kidney angiotensin II and norepinephrine (NE) levels, and enhanced angiotensinogen and angiotensin type 1a receptor gene expression and oxidative stress in renal cortical tissues. Aortic regurgitation rats with renal denervation had decreased albuminuria and glomerular podocyte injury, which were associated with reduced kidney NE, angiotensinogen, angiotensin II, and oxidative stress. Renal denervation combined with olmesartan prevented podocyte injury and albuminuria induced by aortic regurgitation.


In this chronic cardiac volume-overload animal model, activation of the sympathetic nervous system augments kidney renin-angiotensin system and oxidative stress, which act as crucial cardiorenal mediators. Renal denervation and olmesartan prevent the onset and progression of renal injury, providing new insight into the treatment of cardiorenal syndrome.

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