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Sub‐contractile sphingosylphosphorylcholine enhances vasoreactivity via reactive oxygen species
Author(s) -
Ward Jeremy PT,
Aaronson Philip I,
Snetkov Vladimir A
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.863.9
Subject(s) - nadph oxidase , myograph , reactive oxygen species , long term potentiation , hypoxic pulmonary vasoconstriction , chemistry , mesenteric arteries , contraction (grammar) , vasoconstriction , calcium , medicine , endocrinology , biochemistry , biology , artery , receptor
Sphingosylphosphorylcholine (SPC), at concentrations that do not cause contraction (<1uM), causes potentiation of vasoconstriction to other agonists or depolarisation (Snetkov et al, Hypertension 2008;51:239–245). Our objective was to determine whether this was related to activation of NADPH oxidase and production of reactive oxygen species (ROS). METHODS Small pulmonary or mesenteric arteries were mounted on a myograph, challenged with depolarising solutions containing ~23 mM KCl to elicit a small contraction, and incubated with SPC (1uM) before being re‐challenged. RESULTS 0.2 to 1uM SPC caused substantial potentiation of depolarisation‐induced force to between 400 and 800% of control in both rat and mouse arteries. Tempol (3mM) suppressed potentiation (e.g. PA: 526 +/− 220%; +tempol: 200+/−60%, n=5). SPC enhanced ROS production estimated by lucigenin and DCF. Potentiation was abolished in p47phox −/− mice (n=6). 0.2 uM SPC enhanced voltage activated calcium current in whole cell patch by ~30% (p<0.01), and this was mimicked by exogenous ROS. We conclude that low concentrations of SPC may cause hyperreactivity via NADPH oxidase and elevation of ROS, which enhances calcium entry via L‐type channels. Funded by the Wellcome Trust