Protective effects of cariporide on endothelial dysfunction induced by high glucose.
OBJECTIVE
To explore the effects of cariporide, a selective sodium-hydrogen antiporter inhibitor, on endothelial dysfunction induced by high glucose.


METHODS
Acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR), sodium nitroprusside (SNP)-induced endothelium-independent relaxation and biochemical parameters including malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) were measured in rat isolated aorta.


RESULTS
A 6-h incubation of aortic rings with high glucose (44 mmol/L) resulted in a significant inhibition of EDR, but had no effects on endothelium-independent relaxation. After the 6-h incubation of aortic rings in the co-presence of cariporide (0.01, 0.1, and 1 micromol/L) with high glucose, cariporide prevented the inhibition of EDR caused by high glucose in concentration-dependent manners. Similarly, high glucose decreased SOD activity and contents of NO, and increased MDA concentration in aortic tissue. Cariporide (1 micromol/L) significantly resisted the decrease of NO content and SOD activity, and elevation of MDA concentration caused by high glucose in aortic tissues. Mannitol (44 mmol/L) or cariporide (1 micromol/L) alone had no effect on EDR, endothelium-independent relaxation and biochemical parameters.


CONCLUSIONS
Cariporide significantly prevented endothelial dysfunction induced by high glucose. The mechanisms of endothelial dysfunction induced by high glucose may involve the activation of sodium-hydrogen antiporter and the generation of oxygen-free radicals, but it is not related to the change of osmolarity.
Wang
Shuang-xi
SX
Department of Pharmacology, Pharmaceutical College, Central South University, Changsha 410078, China.
Xiong
Xiao-ming
XM
Song
Tao
T
Liu
Li-ying
LY
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013450:Sulfones / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*
D006146:Guanidines; D013450:Sulfones; D009569:Nitric Oxide; D008315:Malondialdehyde; C093373:cariporide; D013482:Superoxide Dismutase; D005947:Glucose