title: Advanced Glycation End Products Impair Voltage-Gated K+ Channels-Mediated Coronary Vasodilation in Diabetic Rats.
abstract: BACKGROUND
  We have previously reported that high glucose impairs coronary vasodilation by reducing voltage-gated K+ (Kv) channel activity. However, the underlying mechanisms remain unknown. Advanced glycation end products (AGEs) are potent factors that contribute to the development of diabetic vasculopathy. The aim of this study was to investigate the role of AGEs in high glucose-induced impairment of Kv channels-mediated coronary vasodilation.
  
  
  METHODS
  Patch-clamp recording and molecular biological techniques were used to assess the function and expression of Kv channels. Vasodilation of isolated rat small coronary arteries was measured using a pressurized myograph. Treatment of isolated coronary vascular smooth muscle cells (VSMCs) and streptozotocin-induced diabetic rats with aminoguanidine, the chemical inhibitor of AGEs formation, was performed to determine the contribution of AGEs.
  
  
  RESULTS
  Incubation of VSMCs with high glucose reduced Kv current density by 60.4 ± 4.8%, and decreased expression of Kv1.2 and Kv1.5 both at the gene and protein level, whereas inhibiting AGEs formation or blocking AGEs interacting with their receptors prevented high glucose-induced impairment of Kv channels. In addition, diabetic rats manifested reduced Kv channels-mediated coronary dilation (9.3 ± 1.4% vs. 36.9 ± 1.4%, P < 0.05), which was partly corrected by the treatment with aminoguanidine (24.4 ± 2.2% vs. 9.3 ± 1.4%, P < 0.05).
  
  
  CONCLUSIONS
  Excessive formation of AGEs impairs Kv channels in VSMCs, then leading to attenuation of Kv channels-mediated coronary vasodilation.
authors.affiliation: Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Wen
authors.initials: W
authors.lastname: Su
authors.affiliation: Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China.
authors.forename: Huirong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000378:metabolism / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology*; D005947:Glucose / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D014664:Vasodilation
chemical_list: D017127:Glycation End Products, Advanced; D024642:Potassium Channels, Voltage-Gated; D005947:Glucose