Na+/H+ exchanger inhibitor prevented endothelial dysfunction induced by high glucose.
The aims of this study were to examine whether cariporide, a selective Na+/H+ exchanger inhibitor, has protective effects against endothelial dysfunction induced by high glucose in vitro and to investigate the potential mechanisms. Exposure of rat aorta rings to high glucose (44 mmol/L) for 6 hours caused an inhibition of acetylcholine-induced endothelium-dependent relaxation but had no effect on sodium nitroprusside-induced endothelium-independent relaxation. Treatment with cariporide (0.01, 0.1, 1 micromol/L) of aortic rings incubated with high-glucose medium attenuated the impaired endothelium-dependent relaxation in a dose-dependent manner. Furthermore, high glucose resulted in an increase of malondialdehyde and a decrease of superoxide dismutase activity in rat aorta rings, and these effects were reversed by cariporide. In addition, cariporide was able to inhibit the activation of Na+/H+ exchanger induced by high glucose in cultured endothelial cells. These findings suggest that the endothelial dysfunction induced by high glucose in vitro is caused by the activation of Na+/H+ exchanger.
Shuang-Xi
Wang
W
Department of Pharmacology, Xiang-Ya Medical College, Central South University, Hunan, People's Republic of China.
Li-Ying
Liu
L
Hu-Min
Yu-Hui
Liu
L
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005947:Glucose / Q000008:administration & dosage*; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000502:physiology; D013450:Sulfones / Q000494:pharmacology*
D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide; D005947:Glucose