Pioglitazone provides beneficial effect in metabolic syndrome rats via affecting intracellular Na+ Dyshomeostasis.

Abstract

Metabolic syndrome, is associated impaired blood glucose level, insulin resistance, and dyslipidemia caused by abdominal obesity. Also, it is related with cardiovascular risk accumulation and cardiomyopathy. The hypothesis of this study was to examine the effect of thiazolidinediones such as pioglitazone on intracellular Na+ homeostasis in heart of metabolic syndrome male rats. Abdominal obesity and glucose intolerance had measured as a marker of metabolic syndrome. Intracellular Na+ concentration ([Na+]i) at rest and [Na+]i during pacing with electrical field stimulation were determined in freshly isolated cardiomyocytes. Also, TTX-sensitive Na+- channel current (INa) density and I-V characteristics of these channels were measured to understand [Na+]i homeostasis. We determined the protein levels of Na+/Ca2+ exchanger and Na+-K+ pump to understand the relation between [Na+]i homeostasis. High sucrose intake significantly increased body mass and blood glucose level of the rats in the metabolic syndrome group as compared with control group. There was a decrease in INa density and there were differences in points on activation curve of INa. Basal [Na+]i in metabolic syndrome group significantly increased but there was a significantly decrease in [Na+]i in stimulated cardiomyocytes in metabolic syndrome. Furthermore, pioglitazone induced decreases in the basal [Na+]i and preserved the decrease in INa and [Na+]i in stimulated cardiomyocytes to those of controls. Histologically, metabolic syndrome affected heart and associated tissues together with many other organs. Results of the present study suggest that pioglitazone has significant beneficial effects on metabolic syndrome associated disturbances in the heart via effecting Na+ homeostasis in cardiomyocytes.