Altered mechanical and electrical activities of the diabetic heart: Possible use of new therapeutics?


TURAN B. , UĞUR M., Ozdemir S., Yaras N.

Experimental and Clinical Cardiology, vol.10, no.3, pp.189-195, 2005 (Journal Indexed in SCI Expanded) identifier

  • Publication Type: Article / Article
  • Volume: 10 Issue: 3
  • Publication Date: 2005
  • Title of Journal : Experimental and Clinical Cardiology
  • Page Numbers: pp.189-195
  • Keywords: Angiotensin II receptors, Antioxidants, Cardiomyopathy, Oxidative stress, Redox signalling, Type I diabetes

Abstract

Diabetes mellitus produces functional, biochemical and morphological myocardial abnormalities independent of coronary atherosclerosis and hypertension. Although tight glycemic control decreases the risk of heart failure in patients with diabetes, the effects of different diabetic treatment regimens on heart failure have yet to be determined and remain subject to further investigation. Evidence suggests that reactive oxygen species play an important role in the development of diabetic cardiomyopathy, and antioxidants have been used to reduce cardiomyopathy in patients with diabetes. Therefore, the present study examines the treatment of streptozotocin-induced diabetic rats with sodium selenite (5 μmol/kg/day, intraperitoneally). The results showed that sodium selenite treatment could restore the altered mechanical and electrical activities of diabetic rat hearts. The results also demonstrate that the beneficial effects of this treatment on diabetic rat heart dysfunction appear to be due to the restoration of diminished K+ currents; the restoration of increased intracellular Ca2+ concentrations in diabetes; and all these beneficial effects are partially related to the restoration of the cell glutathione redox cycle. It has been hypothesized that the angiotensin II (Ang II) signalling pathway may also play a role in the development of diabetic cardiomyopathy. It is the ability of Ang II to produce reactive oxygen species and the involvement of these molecules in signal transduction that are the hallmark of Ang II activation. Although action potential prolongation and diminished K+ currents were reversed by angiotensin receptor type I (AT1) blockers in diabetic rat heart, their effects on Ca2+ homeostasis in diabetic cardiomyocytes are not yet clear. Thus, the effects of AT1 blocker treatment (candesartan cilexetil) on cardiac Ca2+ metabolism, and on the contractile state and electrical activity of papillary muscle in diabetic rats were examined. It was shown that treatment with an AT1 blocker restored the altered kinetics of Ca2+ transients in cardiomyocytes and the contractile activity in papillary muscle strips from diabetic rats. Thus, Ang II receptor blockade protects the heart from the development of cellular alterations that are typically related to diabetes. ©2005 Pulsus Group Inc. All rights reserved.