Modification of Sarcolemmal Ca2+- transport and Na+- K+ ATPase Defects by Propionyl L-Carnitine during the Development of Diabetic Cardiomyopathy

Author(s): Vijayan Elimban, Khushman Kaur, Roberto Ferrari, Naranjan S. Dhalla

Introduction: Since diabetic cardiomyopathy is associated with metabolic abnormalites and subcellular Ca2+- handling defects, this study examined the effects of metabolic therapy with propionyl L-carnitine (PPLC) in modifying diabetes induced changes in cardiac sarcolemma (SL) Ca2+- transport.

Methods: Three days after inducing diabetes by injecting 65 mg/kg streptozotocin, rats were treated with or without PPLC (100 mg/kg; daily) for 8 weeks. These animals were assessed hemodynamically for cardiac function and the activities of some Ca2+-transport systems were determined in cardiac SL preparations.

Results: Improvement of cardiac function in diabetic animals by PPLC was associated with lowering of plasma lipids. Depressions in SL Na+- K+ ATPase and Na+- Ca2+ exchange activities in diabetic herats were partially attenuated by PPLC treatment. Maximal enzyme activities (Vmax values) for control, diabetes and PPLC- treated preparations for Na+-K+ ATPase were 33.61, 18.46 and 27.64 (μmol Pi/mg/hr) whereas maximal Ca2+- accumulation activities (Bmax values) for Na+- Ca2+ exchange were 9.60, 5.09 and 7.65 μΜ Ca2+, respectively. Although both ATP- dependent Ca2+- uptake and Ca2+- stimulated ATPase were depressed in diabetic SL, treatment with PPLC did not show any improvement in these activities. Alterations in different biomarkers of oxidative stress in diabetic heart were attenuated by PPLC treatment.

Conclusions: These results indicate that alterations in SL Na+- K+ ATPase and Na+- Ca2+ exchange activities in diabetic heart may be attenuated by reduction in the development of oxidative stress by PPLC. It is suggested that modifictaion of SL defects by metabolic therapy with PPLC may contribute in reducing the occurence of intracellular Ca2+-overload and improving cardiac function in diabetic cardiomyopathy.