title: Propofol causes vasodilation in vivo via TRPA1 ion channels: role of nitric oxide and BKCa channels.
abstract: BACKGROUND
  Transient receptor potential (TRP) ion channels of the A1 (TRPA1) and V1 (TRPV1) subtypes are key regulators of vasomotor tone. Propofol is an intravenous anesthetic known to cause vasorelaxation. Our objectives were to examine the extent to which TRPA1 and/or TRPV1 ion channels mediate propofol-induced depressor responses in vivo and to delineate the signaling pathway(s) involved.
  
  
  METHODS
  Mice were subjected to surgery under 1.5-2.5% sevoflurane gas with supplemental oxygen. After a stable baseline in mean arterial pressure (MAP) was achieved propofol (2.5, 5.0, 10.0 mg/kg/min) was administered to assess the hemodynamic actions of the intravenous anesthetic. The effect of nitric oxide synthase (NOS) inhibition with L-NAME and/or calcium-gated K+ channel (BKCa) inhibition with Penetrim A (Pen A), alone and in combination, on propofol-induced decreases in mean arterial pressure were assessed in control C57Bl/6J, TRPA1-/-, TRPV1-/- and double-knockout mice (TRPAV-/-).
  
  
  RESULTS
  Propofol decreased MAP in control mice and this effect was markedly attenuated in TRPA1-/- and TRPAV-/- mice but unaffected in TRPV1-/-mice. Moreover, pretreatment with L-NAME or Pen A attenuated the decrease in MAP in control and TRPV1-/- mice, and combined inhibition abolished the depressor response. In contrast, the markedly attenuated propofol-induced depressor response observed in TRPA1-/- and TRPAV-/- mice was unaffected by pre-treatment with Pen A or L-NAME when used either alone or in combination.
  
  
  CONCLUSIONS
  These data demonstrate for the first time that propofol-induced depressor responses in vivo are predominantly mediated by TRPA1 ion channels with no involvement of TRPV1 ion channels and includes activation of both NOS and BKCa channels.
authors.affiliation: Department of Biological Sciences, Kent State University, Kent, Ohio, United States of America.
authors.forename: Sayantani
authors.initials: S
authors.lastname: Sinha
authors.affiliation: Department of Biological Sciences, Kent State University, Kent, Ohio, United States of America.
authors.forename: Pritam
authors.initials: P
authors.lastname: Sinharoy
authors.affiliation: Department of Integrative Medical Sciences, Northeast Ohio Medical College, Rootstown, Ohio, United States of America.
authors.forename: Ian N
authors.initials: IN
authors.lastname: Bratz
authors.affiliation: Department of Biological Sciences, Kent State University, Kent, Ohio, United States of America.
authors.forename: Derek S
authors.initials: DS
authors.lastname: Damron
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005260:Female; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000502:physiology*; D015742:Propofol / Q000494:pharmacology*; D015398:Signal Transduction; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: C530995:BKCa protein, mouse; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D014665:Vasodilator Agents; D009569:Nitric Oxide; D015742:Propofol
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