Eplerenone reduces arterial thrombosis in diabetic rats

J Renin Angiotensin Aldosterone Syst. 2015 Dec;16(4):1085-94. doi: 10.1177/1470320313515037. Epub 2014 Jul 16.

Abstract

Introduction: Clinical studies demonstrated the benefits of eplerenone (EPL) in reduction of cardiovascular events in diabetic patients. Since acute myocardial infarction (AMI) and stroke are related to acute intravascular thrombosis, we postulate that the beneficial effects of EPL may result from its antithrombotic action.

Materials and methods: Streptozotocin (STZ)-induced diabetic rats were treated with EPL (100 mg/kg/day) for 10 days. Thrombosis in the carotid artery was stimulated electrically.

Results: Thrombosis development was enhanced in STZ-induced diabetic rats as compared to normoglycaemic controls. EPL caused prolongation of the time to artery occlusion, reduction in the incidence of occlusion and decrease in thrombus weight. Changes in the thrombi structure and the inhibition of hypertrophy of the tunica media in the artery wall were also observed. EPL caused reduction in tissue factor, plasminogen activator inhibitor type 1 and interleukin-1β plasma levels.

Conclusions: Our study demonstrated the antithrombotic effect of EPL manifested by a decrease in the dynamics of thrombus formation and changes in its structure. The changes in thrombosis process were accompanied by antihaemostatic, profibrinolytic and anti-inflammatory effects. The aldosterone blockade with EPL seems to be an additional pharmacological strategy for the prevention and treatment of thrombotic disorders in diabetes.

Keywords: Eplerenone; aldosterone; arterial thrombosis; diabetes; rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carotid Arteries / drug effects
  • Carotid Arteries / physiopathology
  • Diabetes Mellitus, Experimental / complications*
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / physiopathology
  • Eplerenone
  • Hemostasis / drug effects
  • Interleukins / metabolism
  • Male
  • Rats, Wistar
  • Regional Blood Flow / drug effects
  • Spironolactone / analogs & derivatives*
  • Spironolactone / pharmacology
  • Spironolactone / therapeutic use
  • Thrombosis / blood
  • Thrombosis / drug therapy*
  • Thrombosis / pathology
  • Thrombosis / physiopathology
  • Vascular Patency / drug effects

Substances

  • Interleukins
  • Spironolactone
  • Eplerenone