Na+/Ca2+ exchanger inhibitor ameliorates impaired endothelium-dependent Na+ relaxation induced by high glucose in rat aorta.
The present study was designed to investigate the effects of KB-R7943, an inhibitor of the Na+/Ca2+ exchanger, on impaired endothelium-dependent relaxation (EDR) induced by high glucose in rat isolated aorta. Both acetylcholine (ACh)-induced EDR and sodium nitroprusside (SNP)-induced endothelium-independent relaxation (EIR) were measured after aortic rings had been exposed to high glucose in the absence and presence of KB-R7943. Coincubation of aortic rings with high glucose (25 mmol/L) for 24 h resulted in a significant inhibition of EDR, but had no effect on EIR. After incubation of aortic rings in the presence of both KB-R7943 (0.1-10 micromol/L) and high glucose for 24 h, significantly attenuation of impaired EDR was observed. This protective effect of KB-R7943 (10 micromol/L) was abolished by superoxide dismutase (SOD; 200 U/mL) and l-arginine (3 mmol/L), whereas d-arginine (3 mmol/L) had no effect. Similarly, high glucose decreased SOD activity and the release of nitric oxide (NO) and increased superoxide anion (O2(-)) production in aortic tissue. KB-R7943 significantly decreased O2(-) production and increased SOD activity and NO release. These results suggest that KB-R7943 can restore impaired EDR induced by high glucose in rat isolated aorta, which may be related to the scavenging of oxygen free radicals and enhanced NO production.
Su
Ying
Y
Department of Endocrinology, The First Clinical Hospital of Harbin Medical University, Harbin, China.
Liu
Xiao-Min
XM
Sun
Yan-Ming
YM
Jin
Hong-Bo
HB
Luan
Ying
Y
Wu
Yun
Y
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D005947:Glucose / Q000008:administration & dosage* / Q000633:toxicity; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000502:physiology*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; C110927:Slc8a2 protein, rat; D019831:Sodium-Calcium Exchanger; D013890:Thiourea; D005947:Glucose