title: The molecular pathway of ATP-sensitive potassium channel in endothelial cells for mediating arteriole relaxation.
abstract: OBJECTIVE
  The endothelial molecular pathway of a new ATP-sensitive potassium channel (KATP) opener natakalim was investigated in mesenteric arterioles of rats.
  
  
  METHODS
  A DMT wire myograph was used to evaluate the vasorelaxation effects of natakalim. Ca(2+) responses of endothelial cells induced by natakalim were measured by laser confocal fluorescence microscopy. NO assay kits and Western blotting were used.
  
  
  RESULTS
  The new KATP opener natakalim significantly produced endothelium-dependent arteriolar dilation and increased endothelial cell intracellular calcium concentration ([Ca(2+)]i) as well as NO release, which could be inhibited by SB366791 and capsazepine, the specific TRPV1 blockers. Additionally, down-regulation of endothelial TRPV1 by RNA interference inhibited the Ca(2+) influx induced by natakalim.
  
  
  CONCLUSIONS
  These results suggest that endothelial KATP mediated natakalim-induced vasorelaxation through increasing [Ca(2+)]i and NO production. Activation of endothelial TRPV1 channels and subsequent Ca(2+) entry, and NO release at least partly contribute to endothelium-dependent vasorelaxation induced by natakalim.
authors.affiliation: Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Chen
authors.affiliation: Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Han
authors.affiliation: Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Cardiovascular Drug Research Center, Thadweik Academy of Medicine, Beijing 100039, China.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Cui
authors.affiliation: Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Pan
authors.affiliation: Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.affiliation: Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850, China. Electronic address: longchaoliang@sohu.com.
authors.forename: Chaoliang
authors.initials: C
authors.lastname: Long
authors.affiliation: Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850, China; Cardiovascular Drug Research Center, Thadweik Academy of Medicine, Beijing 100039, China. Electronic address: wh9588@sina.com.
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
mesh_terms: D000498:Allyl Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D002934:Cinnamates / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011437:Propylamines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D050916:TRPV Cation Channels / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D000498:Allyl Compounds; D000813:Anilides; D002934:Cinnamates; D054086:KATP Channels; C477659:N-(3-methoxyphenyl)-4-chlorocinnamanilide; D011437:Propylamines; D034741:RNA, Small Interfering; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C556401:natakalim; D009569:Nitric Oxide; C071423:capsazepine; D002211:Capsaicin; D002118:Calcium
keywords: Intracellular calcium concentration; Natakalim; Nitric oxide; Transient receptor potential vanilloid 1