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Journal of Diabetes Research
Volume 2013, Article ID 427693, 14 pages
http://dx.doi.org/10.1155/2013/427693
Research Article

RU28318, an Aldosterone Antagonist, in Combination with an ACE Inhibitor and Angiotensin Receptor Blocker Attenuates Cardiac Dysfunction in Diabetes

1Department of Pharmacology & Toxicology, Faculty of Medicine, Kuwait University, P.O. Box 24923, 13110 Safat, Kuwait
2Department of Physiology, Faculty of Medicine, Kuwait University, P.O. Box 24923, 13110 Safat, Kuwait
3Department of Medicine, Faculty of Medicine, Kuwait University, P.O. Box 24923, 13110 Safat, Kuwait

Received 25 April 2013; Revised 16 July 2013; Accepted 17 July 2013

Academic Editor: Daisuke Koya

Copyright © 2013 Ibrahim F. Benter et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Aims. We evaluated the effects of RU28318 (RU), a selective mineralocorticoid receptor (MR) antagonist, Captopril (Capt), an angiotensin converting enzyme inhibitor, and Losartan (Los), an angiotensin receptor blocker, alone or in combination with ischemia/reperfusion- (I/R-) induced cardiac dysfunction in hearts obtained from normal and diabetic rats. Methods. Isolated hearts were perfused for 30 min and then subjected to 30 min of global ischemia (I) followed by a period of 30 min of reperfusion (R). Drugs were administered for 30 min either before or after ischemia. Drug regimens tested were RU, Capt, Los, RU + Capt, RU + Los, Capt + Los, and RU + Capt + Los (Triple). Recovery of cardiac hemodynamics was evaluated. Results. Recovery of cardiac function was up to 5-fold worse in hearts obtained from diabetic animals compared to controls. Treatment with RU was generally better in preventing or reversing ischemia-induced cardiac dysfunction in normal hearts compared to treatment with Capt or Los alone. In diabetic hearts, RU was generally similarly effective as Capt or Los treatment. Conclusions. RU treatment locally might be considered as an effective therapy or preventative measure in cardiac I/R injury. Importantly, RU was the most effective at improving (a measure of diastolic function) when administered to diabetic hearts after ischemia.