BACKGROUND: We have previously reported that high @entity413 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 @entity532 . The aim of this study was to investigate the role of AGEs in high @entity413 -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 @entity35 small coronary arteries was measured using a pressurized myograph. Treatment of isolated coronary vascular smooth muscle cells (VSMCs) and @entity3839 -induced @entity6 @entity35 with @entity5118 , the chemical inhibitor of AGEs formation, was performed to determine the contribution of AGEs. RESULTS: Incubation of VSMCs with high @entity413 reduced Kv current density by 60.4    4.8%, and decreased expression of Kv1.2 and @entity22926 both at the gene and protein level, whereas inhibiting AGEs formation or blocking AGEs interacting with their receptors prevented high @entity413 -induced impairment of Kv channels. In addition, @entity6 @entity35 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 @entity5118 (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.

Advanced Glycation End Products Impair Voltage-Gated K+ Channels-Mediated Coronary Vasodilation in XXXX @entity35 .

@entity5118 :: ('MESH:C004479', 'Chemical') :: ['aminoguanidine'] @entity6 :: ('MESH:D003920', 'Disease') :: ['diabetic'] @entity22926 :: ('25470(Tax:10116)', 'Gene') :: ['Kv1.5'] @entity3839 :: ('MESH:D013311', 'Chemical') :: ['streptozotocin'] @entity532 :: ('MESH:D003925', 'Disease') :: ['diabetic vasculopathy'] @entity35 :: ('10116', 'Species') :: ['rat', 'rats'] @entity413 :: ('MESH:D005947', 'Chemical') :: ['glucose']
@entity6 :: (MESH:D003920,Disease) :: ['Diabetic']
