Exp Clin Endocrinol Diabetes 2014; 122 - OP2_06
DOI: 10.1055/s-0034-1371981

Influence of a mineralocorticoid receptor blockade on vascular function in atherosclerotic mouse models under high-fat diet

C Brunssen 1, J Rissler 1, H Langbein 1, A Hofmann 1, A Deussen 2, M Peitzsch 3, P Cimalla 4, E Koch 4, G Eisenhofer 3, H Morawietz 1
  • 1University Hospital Carl Gustav Carus, Department of Medicine III, Division of Vascular Endothelium and Microcirculation, Dresden, Germany
  • 2Dresden University of Technology, Medical Faculty Carl Gustav Carus, Department of Physiology, Dresden, Germany
  • 3University Hospital Carl Gustav Carus, Department of Medicine III, Institute of Clinical Chemistry and Laboratory Medicine, Dresden, Germany
  • 4Dresden University of Technology, Medical Faculty Carl Gustav Carus, Department of Clinical Sensoring and Monitoring, Dresden, Germany

An important step in the pathogenesis of atherosclerosis is the development of endothelial dysfunction. One risk factor of endothelial dysfunction is consumption of high amounts of saturated fat. Recent studies reveal an endothelium-protective effect of blockade of the aldosterone-binding mineralocorticoid receptor (MR). In this study, we analysed the effects of high-fat diet (HFD) and MR blockade on metabolic parameters and endothelial function in mouse models of atherosclerosis.

Body weight and the amount of epididymal, retroperitoneal, mesenteric and perivascular fat were increased after HFD. Diet-induced obesity elevated blood glucose, triglyceride, total cholesterol, and LDL plasma levels of all mice strains. Body weight of wildtype animals fed the HFD+MR blocker eplerenone was reduced compared to the HFD control group. Eplerenone was detectable in plasma and liver of wildtype mice. Aldosterone concentrations were increased in plasma of eplerenone-fed wildtype mice. HFD-fed atherosclerotic mice (LDLR-/-, LOX1tg and LOLR as combination of LOX1tg/LDLR-/-) showed elevated fasting blood glucose levels compared to standard diet (STD)-fed mice after fasting. Treatment with eplerenone normalized blood glucose levels. Vascular function was analysed by Mulvany myograph. LDLR-/-, LOX-1tg and LOLR mice showed decreased endothelial function compared to wildtype mice under STD. In response to HFD we could observe a decreased endothelial function in wildtype mice. LOX-1tg and LOLR mice showed stronger pronounced endothelial dysfunction under HFD. In these experiments, eplerenone shows beneficial effects. This could be due to the reduced production of reactive oxygen species measured after eplerenone medication. In addition, endothelial function was analysed in vivo by self-developed optical coherence tomography.

In conclusion, our study provides improved understanding of the effects of MR inhibition on high-fat diet induced endothelial dysfunction and metabolic parameters.