| Autor: |
Tappia PS; Institute of Cardiovascular Sciences, and Asper Clinical Research Institute, St. Boniface Hospital, Winnipeg, MB R2H 2A6, Canada., Elimban V; Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada.; Department of Physiology and Pathophysiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, Canada., Shah AK; Department of Nutrition and Food Sciences, California State University, Los Angeles, CA 90032, USA., Goyal RK; Department of Pharmacology, Delhi Pharmaceutical Sciences and Research University, New Delhi 110017, India., Dhalla NS; Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada.; Department of Physiology and Pathophysiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, Canada. |
| Abstrakt: |
In order to investigate the subcellular mechanisms underlying the beneficial effects of sarpogrelate-a 5-HT 2A receptor antagonist-on diabetic cardiomyopathy, diabetes was induced in rats by injecting streptozotocin (65 mg/kg). Diabetic animals were treated with or without sarpogrelate (5 mg/kg daily) for 6 weeks; diabetic animals were also treated with insulin (10 units/kg daily) for comparison. Elevated plasma levels of glucose and lipids, depressed insulin levels, hemodynamic alterations and cardiac dysfunction in diabetic animals were partially or fully attenuated by sarpogrelate or insulin treatment. Diabetes-induced changes in myocardial high-energy phosphate stores, as well as depressed mitochondrial oxidative phosphorylation and Ca 2+ -uptake activities, were significantly prevented by these treatments. Reductions in sarcolemma Na + -K + ATPase, Na + -Ca 2+ exchange, Ca 2+ -channel density and Ca 2+ -uptake activities were also attenuated by treatments with sarpogrelate and insulin. In addition, decreases in diabetes-induced sarcoplasmic reticulum Ca 2+ -uptake, Ca 2+ -release and Ca 2+ -stimulated ATPase activities, myofibrillar Mg 2+ -ATPase and Ca 2+ -stimulated ATPase activities, and myosin Mg 2+ -ATPase and Ca 2+ -ATPase activities were fully or partially prevented by sarpogrelate and insulin treatments. Marked alterations in different biomarkers of oxidative stress, such as malondialdehyde, superoxide dismutase and glutathione peroxidase, in diabetic hearts were also attenuated by treating the animals with sarpogrelate or insulin. These observations suggest that therapy with sarpogrelate, like that with insulin, may improve cardiac function by preventing subcellular and metabolic defects as a consequence of a reduction in oxidative stress. |
