title: Modulation of gap-junction-dependent arterial relaxation by ascorbic acid.
abstract: OBJECTIVE
  To investigate whether ascorbic acid (AA) can influence endothelium-dependent relaxation by modulating the spread of endothelial hyperpolarization through the arterial wall via gap junctions.
  
  
  METHODS
  Force development and membrane potential were monitored by myography and sharp electrode techniques in isolated rabbit iliac arteries.
  
  
  RESULTS
  AA prevented the ability of the gap junction blocker 2-aminoethoxydiphenyl borate to inhibit endothelium-dependent relaxations and subintimal smooth muscle hyperpolarizations evoked by cyclopiazonic acid in the presence of nitric oxide (NO) synthase and cyclooxygenase blockade. AA also prevented the ability of a connexin-mimetic peptide targeted against Cx37 and Cx40 (37,40Gap 26) to attenuate the transmission of endothelial hyperpolarization to subintimal smooth muscle, and a peptide targeted against Cx43 (43Gap 26) to attenuate the spread of subintimal hyperpolarization to subadventitial smooth muscle and the associated mechanical relaxation. Parallel studies with endothelium-denuded preparations demonstrated that AA and cyclopiazonic acid both depressed relaxation evoked by the NO donor MAHMA NONOate.
  
  
  CONCLUSIONS
  The data suggest that AA can modulate arterial function through a previously unrecognized ability to preserve electrotonic signalling via myoendothelial and homocellular smooth muscle gap junctions under conditions where cell coupling is depressed. Underlying mechanisms do not involve amplification of 'residual' NO activity by AA.
authors.affiliation: Department of Diagnostic Radiology, Wales Heart Research Institute, Cardiff University, Cardiff, UK.
authors.forename: David H
authors.initials: DH
authors.lastname: Edwards
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chaytor
authors.forename: Linda M
authors.initials: LM
authors.lastname: Bakker
authors.forename: Tudor M
authors.initials: TM
authors.lastname: Griffith
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001896:Boron Compounds / Q000494:pharmacology; D018031:Connexin 43 / Q000037:antagonists & inhibitors / Q000502:physiology; D017630:Connexins / Q000037:antagonists & inhibitors / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D017629:Gap Junctions / Q000502:physiology*; D006834:Hydrazines / Q000494:pharmacology; D007083:Iliac Artery / Q000187:drug effects* / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects*; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein
chemical_list: D001205:Ascorbic Acid; D001896:Boron Compounds; D018031:Connexin 43; D017630:Connexins; D006834:Hydrazines; D007211:Indoles; D007213:Indomethacin; D020030:Nitric Oxide Donors; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside; D010069:Oxadiazoles; D010656:Phenylephrine; D011810:Quinoxalines; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein; C105785:1-hexanamine-6-(2-hydroxy-1-methyl-2-nitrosohydrazine)-N-methyl; C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; C109986:2-aminoethoxydiphenyl borate; C000543:cyclopiazonic acid