title: H2O2 is the transferrable factor mediating flow-induced dilation in human coronary arterioles.
abstract: BACKGROUND
  Endothelial derived hydrogen peroxide (H(2)O(2)) is a necessary component of the pathway regulating flow-mediated dilation (FMD) in human coronary arterioles (HCAs). However, H(2)O(2) has never been shown to be the endothelium-dependent transferrable hyperpolarization factor (EDHF) in response to shear stress.
  
  
  OBJECTIVE
  We examined the hypothesis that H(2)O(2) serves as the EDHF in HCAs to shear stress.
  
  
  RESULTS
  Two HCAs were cannulated in series (a donor intact vessel upstream and endothelium-denuded detector vessel downstream). Diameter changes to flow were examined in the absence and presence of polyethylene glycol catalase (PEG-CAT). The open state probability of large conductance Ca(2+)-activated K(+) (BK(Ca)) channels in smooth muscle cells downstream from the perfusate from an endothelium-intact arteriole was examined by patch clamping. In some experiments, a cyanogen bromide-activated resin column bound with CAT was used to remove H(2)O(2) from the donor vessel. When flow proceeds from donor to detector, both vessels dilate (donor:68±7%; detector: 45±11%). With flow in the opposite direction, only the donor vessel dilates. PEG-CAT contacting only the detector vessel blocked FMD in that vessel (6±4%) but not in donor vessel (61±13%). Paxilline inhibited dilation of endothelium-denuded HCAs to H(2)O(2). Effluent from donor vessels elicited K(+) channel opening in an iberiotoxin- or PEG-CAT-sensitive fashion in cell-attached patches but had little effect on channel opening on inside-out patches. Vasodilation of detector vessels was diminished when exposed to effluent from CAT-column.
  
  
  CONCLUSIONS
  Flow induced endothelial production of H(2)O(2), which acts as the transferrable EDHF activating BK(Ca) channels on the smooth muscle cells.
authors.affiliation: Office of Research, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Liu
authors.forename: Aaron H
authors.initials: AH
authors.lastname: Bubolz
authors.forename: Suelhem
authors.initials: S
authors.lastname: Mendoza
authors.forename: David X
authors.initials: DX
authors.lastname: Zhang
authors.forename: David D
authors.initials: DD
authors.lastname: Gutterman
mesh_terms: D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001685:Biological Factors / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011092:Polyethylene Glycols / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012039:Regional Blood Flow / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D001685:Biological Factors; D007211:Indoles; D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; C070295:catalase-polyethylene glycol; C067410:endothelium-dependent hyperpolarization factor; C048220:paxilline; D011092:Polyethylene Glycols; D006861:Hydrogen Peroxide; D002374:Catalase