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Empagliflozin decreases myocardial cytoplasmic Na through inhibition of the cardiac Na/H exchanger in rats and rabbits.
- Source :
- Diabetologia; Mar2017, Vol. 60 Issue 3, p568-573, 6p, 2 Graphs
- Publication Year :
- 2017
-
Abstract
- Aims/hypothesis: Empagliflozin (EMPA), an inhibitor of the renal sodium-glucose cotransporter (SGLT) 2, reduces the risk of cardiovascular death in patients with type 2 diabetes. The underlying mechanism of this effect is unknown. Elevated cardiac cytoplasmic Na ([Na]) and Ca ([Ca]) concentrations and decreased mitochondrial Ca concentration ([Ca]) are drivers of heart failure and cardiac death. We therefore hypothesised that EMPA would directly modify [Na], [Ca] and [Ca] in cardiomyocytes. Methods: [Na] [Ca], [Ca ] and Na/H exchanger (NHE) activity were measured fluorometrically in isolated ventricular myocytes from rabbits and rats. Results: An increase in extracellular glucose, from 5.5 mmol/l to 11 mmol/l, resulted in increased [Na] and [Ca] levels. EMPA treatment directly inhibited NHE flux, caused a reduction in [Na] and [Ca] and increased [Ca]. After pretreatment with the NHE inhibitor, Cariporide, these effects of EMPA were strongly reduced. EMPA also affected [Na] and NHE flux in the absence of extracellular glucose. Conclusions/interpretation: The glucose lowering kidney-targeted agent, EMPA, demonstrates direct cardiac effects by lowering myocardial [Na] and [Ca] and enhancing [Ca], through impairment of myocardial NHE flux, independent of SGLT2 activity. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0012186X
- Volume :
- 60
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Diabetologia
- Publication Type :
- Academic Journal
- Accession number :
- 121186028
- Full Text :
- https://doi.org/10.1007/s00125-016-4134-x