title: Advanced glycation end products impair K(Ca)3.1- and K(Ca)2.3-mediated vasodilatation via oxidative stress in rat mesenteric arteries.
abstract: The present study was designed to investigate the role of advanced glycation end products (AGEs) in intermediate-conductance and small-conductance Ca(2+)-activated potassium channels (KCa3.1 and KCa2.3)-mediated relaxation in rat resistance arteries and the underlying mechanism. The endothelial function of mesenteric arteries was assessed with the use of wire myography. Expression levels of KCa3.1 and KCa2.3 were measured by using Western blot. Reactive oxygen species (ROS) were measured by using dihydroethidium and 2', 7'-dichlorofluorescein diacetate. KCa3.1 and KCa2.3-mediated vasodilatation responses to acetylcholine and NS309 (opener of KCa3.1 and KCa2.3) were impaired by incubation of the third-order mesenteric arteries from normal rats with AGEs (200 μg ml(-1) for 3 h). In cultured human umbilical vein endothelial cells (HUVECs), AGEs increased ROS level and decreased the protein expression of KCa3.1 and KCa2.3. Antioxidant alpha lipoic acid restored the impairment in both vasodilatation function and expression of KCa3.1 and KCa2.3. H2O2 could mimic the effect of AGEs on the protein expression of KCa3.1 and KCa2.3 in cultured HUVECs. These results demonstrate for the first time that AGEs impaired KCa3.1 and KCa2.3-mediated vasodilatation in rat mesenteric arteries via downregulation of both KCa3.1 and KCa2.3, in which the enhanced oxidative stress was involved.
authors.affiliation: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, 76 West Yanta Road, Xi'an, 710061, Shaanxi, China.
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Zhao
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiao-Zhen
authors.initials: XZ
authors.lastname: Ma
authors.forename: Nan-Ping
authors.initials: NP
authors.lastname: Wang
authors.forename: Xiu-Ling
authors.initials: XL
authors.lastname: Deng
mesh_terms: D000473:Alkanes / Q000494:pharmacology; D000818:Animals; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D066298:In Vitro Techniques; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000096:biosynthesis / Q000187:drug effects*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*; D011720:Pyrazoles / Q000494:pharmacology; D011806:Quinolinium Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000096:biosynthesis / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: C110349:6,10-diaza-3(1,3),8(1,4)dibenzena-1,5(1,4)diquinolinacyclodecaphane; D000473:Alkanes; D017127:Glycation End Products, Advanced; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C491575:Kcnn4 protein, rat; D011720:Pyrazoles; D011806:Quinolinium Compounds; D051640:Small-Conductance Calcium-Activated Potassium Channels; C411671:TRAM 34; D019331:NG-Nitroarginine Methyl Ester