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Eplerenone prevents salt-induced vascular stiffness in Zucker diabetic fatty rats: a preliminary report

Markus Resch1*, Peter Schmid1, Kerstin Amann2, Sabine Fredersdorf1, Joachim Weil3, Christian Schach1, Christoph Birner1, Daniel P Griese4, Peter Kreuzer1, Sabine Brunner1, Andreas Luchner1, Günter AJ Riegger1 and Dierk H Endemann1*

Author Affiliations

1 Department of Internal Medicine II, Regensburg University Medical Center, Franz Josef Strauss Allee 11, 93053 Regensburg, Germany

2 Department of Nephropathology, University Hospital Erlangen, Universitätsstr. 22, 91054 Erlangen, Germany

3 Medical Clinic II - Cardiology, University Hospital Schleswig Holstein Campus Lübeck, Ratzeburger Alle 160, 23538 Lübeck, Germany

4 Department of Cardiology, Herz- und Gefäßklinik GmbH Bad Neustadt an der Saale, Salzburger Leite 1, 97616 Bad Neustadt an der Saale, Germany

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Cardiovascular Diabetology 2011, 10:94  doi:10.1186/1475-2840-10-94

Published: 18 October 2011



Aldosterone levels are elevated in a rat model of type 2 diabetes mellitus, the Zucker Diabetic fatty rat (ZDF). Moreover blood pressure in ZDF rats is salt-sensitive. The aim of this study was to examine the effect of the aldosterone antagonist eplerenone on structural and mechanical properties of resistance arteries of ZDF-rats on normal and high-salt diet.


After the development of diabetes, ZDF animals were fed either a normal salt diet (0.28%) or a high-salt diet (5.5%) starting at an age of 15 weeks. ZDF rats on high-salt diet were randomly assigned to eplerenone (100 mg/kg per day, in food) (ZDF+S+E), hydralazine (25 mg/kg per day) (ZDF+S+H), or no treatment (ZDF+S). Rats on normal salt-diet were assigned to eplerenone (ZDF+E) or no treatment (ZDF). Normoglycemic Zucker lean rats were also divided into two groups receiving normal (ZL) or high-salt diet (ZL+S) serving as controls. Systolic blood pressure was measured by tail cuff method. The experiment was terminated at an age of 25 weeks. Mesenteric resistance arteries were studied on a pressurized myograph. Specifically, vascular hypertrophy (media-to-lumen ratio) and vascular stiffness (strain and stress) were analyzed. After pressurized fixation histological analysis of collagen and elastin content was performed.


Blood pressure was significantly higher in salt-loaded ZDF compared to ZDF. Eplerenone and hydralazine prevented this rise similarily, however, significance niveau was missed. Media-to-lumen ratio of mesenteric resistance arteries was significantly increased in ZDF+S when compared to ZDF and ZL. Both, eplerenone and hydralazine prevented salt-induced vascular hypertrophy. The strain curve of arteries of salt-loaded ZDF rats was significantly lower when compared to ZL and when compared to ZDF+S+E, but was not different compared to ZDF+S+H. Eplerenone, but not hydralazine shifted the strain-stress curve to the right indicating a vascular wall composition with less resistant components. This indicates increased vascular stiffness in salt-loaded ZDF rats, which could be prevented by eplerenone but not by hydralazine. Collagen content was increased in ZL and ZDF rats on high-salt diet. Eplerenone and hydralazine prevented the increase of collagen content. There was no difference in elastin content.


Eplerenone and hydralazine prevented increased media-to-lumen ratio in salt-loaded ZDF-rats, indicating a regression of vascular hypertrophy, which is likely mediated by the blood pressure lowering-effect. Eplerenone has additionally the potential to prevent increased vascular stiffness in salt-loaded ZDF-rats. This suggests an effect of the specific aldosterone antagonist on adverse vascular wall remodelling.