title: KB-R7943 restores endothelium-dependent relaxation induced by advanced glycosylation end products in rat aorta.
abstract: OBJECTIVE
  The aims of this study were to examine the effects of KB-R7943, an inhibitor of Na(+)/Ca(2+) exchanger, on impaired endothelium-dependent relaxation (EDR) induced by advanced glycosylation end products (AGE) in isolated rat aorta.
  
  
  METHODS
  Both acetylcholine (ACh)-induced EDR and sodium nitroprusside (SNP)-induced endothelium-independent relaxation (EIR) were measured after the rings were exposed to AGE in the absence and presence of KB-R7943.
  
  
  RESULTS
  Co-incubation of aortic rings with AGE (0.1 g/L) for 24 h resulted in a significant inhibition of EDR, but had no effects on EIR. After incubation of the rings in the co-presence of KB-R7943 (0.1-10 μM) with AGE for 24 h, KB-R7943 (10 μM) significantly attenuated impaired EDR. Superoxide dismutase (200 U/mL) and l-arginine (3mM) could ameliorate the impairment of EDR caused by AGE, whereas d-arginine (3mM) had no effect on EDR. Similarly, AGE decreased superoxide dismutase (SOD) activity and the release of nitric oxide (NO), and increased superoxide anion (O(2)(.-)) production in aortic tissue. KB-R7943 (10 μM) significantly decreased O(2)(.-) production and increased SOD activity and the NO release.
  
  
  CONCLUSIONS
  These results suggest that KB-R7943 attenuated the impairment of EDR elicited by AGE partially through scavenging oxygen free radicals.
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Su
authors.forename: Nan
authors.initials: N
authors.lastname: Mao
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Xia
authors.initials: X
authors.lastname: Dong
authors.forename: Fan-Zhen
authors.initials: FZ
authors.lastname: Lin
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Yan-Bo
authors.initials: YB
authors.lastname: Li
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D000889:Anti-Arrhythmia Agents; D017127:Glycation End Products, Advanced; D013890:Thiourea; D005947:Glucose