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

• Published in: Cardiovascular diabetology 2011-10, Vol.10 (1), p.94-94
• Main Authors: Resch, Markus, Schmid, Peter, Amann, Kerstin, Fredersdorf, Sabine, Weil, Joachim, Schach, Christian, Birner, Christoph, Griese, Daniel P, Kreuzer, Peter, Brunner, Sabine, Luchner, Andreas, Riegger, Günter A J, Endemann, Dierk H
• Format: Article
• Language: English
• Subjects: Animals; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - pathology; Diabetes Mellitus, Type 2 - physiopathology; Hypertension; Male; Medical research; Original Investigation; Rats; Rats, Zucker; Rodents; Sodium Chloride, Dietary - adverse effects; Spironolactone - analogs & derivatives; Spironolactone - pharmacology; Spironolactone - therapeutic use; Vascular Resistance - drug effects; Vascular Resistance - physiology; Vascular Stiffness - drug effects; Vascular Stiffness - physiology; Veins & arteries
• ISSN: 1475-2840; 1475-2840
• DOI: 10.1186/1475-2840-10-94

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-