| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2964217 | Journal of Cardiothoracic-Renal Research | 2006 | 8 Pages |
SummaryBackgroundCardiac complications have been demonstrated as a major cause of morbidity and mortality in the diabetic population. However, the mechanisms underlying diabetes-induced cardiomyopathy remain unclear. We tested the hypothesis that endothelin-1 (ET-1) plays an important role in diabetes-induced pathogenesis of ventricular myocyte dysfunction.MethodsDiabetic rat was induced by an intravenous injection of streptozotocin (STZ). The potential contribution of endothelin to diabetic cardiomyopathy was determined by chronic treatment of rats with the ET-1 receptor antagonist, bosentan. Myocyte contractility and intracellular calcium homeostasis were compared using an edge detection/micro-fluorescent system.ResultsVentricular myocytes isolated from diabetic rats exhibited significant depression in cell contractility and altered intracellular Ca2+ ([Ca2+]i) transient. On the other hand, L-type Ca2+ channel activity in diabetic myocytes was not altered. Bosentan treatment successfully prevented myocyte contractile dysfunction and [Ca2+]i depression in diabetic rats without affecting myocyte function from control rats. Bosentan had no effect on Ca2+ channel activity in myocytes obtained from both control and diabetic rats.ConclusionThese data demonstrate that elevated ET-1 in diabetic animals plays an important role in the diabetes-induced cardiac myocyte dysfunction. Blockade of ET-1 receptor may be a potential therapeutic strategy in the treatment of diabetes-induced heart failure.
