Protective effects of the sodium/calcium exchanger inhibitor on endothelial dysfunction induced by high glucose

Exp Clin Endocrinol Diabetes. 2015 Jan;123(1):7-10. doi: 10.1055/s-0034-1385924. Epub 2014 Aug 22.

Abstract

This study was designed to investigate the protective effects of KB-R7943, an inhibitor of sodium/calcium exchanger (NCX) on endothelial dysfunction induced by high glucose in endothelial cells. NCX expression, NCX activity and oxidative stress index were determined after endothelial cells were exposed to high glucose in the absence and presence of KB-R7943. Coincubation of endothelial cells with high glucose for 6, 12, 24 and 48 h resulted in a significant decrease in NCX expression, superoxide dismutase (SOD) activity and the release of nitric oxide (NO), and increased NCX activity and malondialdehyde (MDA) production. These effects were abolished by KB-R7943. A similar effect was observed after treatment of endothelial cells with H-7, a protein kinase C (PKC) inhibitor and NADPH oxidase inhibitor (DPI). These results suggest that the sodium/calcium exchanger inhibitor exerts beneficial effects on high glucose-induced endothelial dysfunction, which may be related to PKC signal pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • Anti-Arrhythmia Agents / pharmacology*
  • Enzyme Inhibitors / pharmacology
  • Glucose / adverse effects*
  • Glucose / pharmacology
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Human Umbilical Vein Endothelial Cells / pathology
  • Humans
  • Malondialdehyde / metabolism
  • NADPH Oxidases / antagonists & inhibitors
  • NADPH Oxidases / metabolism
  • Nitric Oxide / metabolism
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Signal Transduction / drug effects
  • Sodium-Calcium Exchanger / antagonists & inhibitors*
  • Sodium-Calcium Exchanger / metabolism
  • Superoxide Dismutase / antagonists & inhibitors
  • Superoxide Dismutase / metabolism
  • Sweetening Agents / adverse effects*
  • Sweetening Agents / pharmacology
  • Thiourea / analogs & derivatives*
  • Thiourea / pharmacology

Substances

  • 2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate
  • Anti-Arrhythmia Agents
  • Enzyme Inhibitors
  • Sodium-Calcium Exchanger
  • Sweetening Agents
  • Nitric Oxide
  • Malondialdehyde
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Superoxide Dismutase
  • NADPH Oxidases
  • Protein Kinase C
  • Thiourea
  • Glucose