title: Early vasodilator response to anodal current application in human is not impaired by cyclooxygenase-2 blockade.
abstract: It is generally acknowledged that cutaneous vasodilatation in response to monopolar galvanic current application would result from an axon reflex in primary afferent fibers and the neurogenic inflammation resulting from neuropeptide release. Previous studies suggested participation of prostaglandin (PG) in anodal current-induced cutaneous vasodilatation. Thus the inducible cyclooxygenase (COX) isoform (COX-2), assumed to play a key role in inflammation, should be involved in the synthesis of the PG that is released. Skin blood flow (SkBF) variations induced by 5 min of 0.1-mA monopolar anodal current application were evaluated with laser-Doppler flowmetry on the forearm of healthy volunteers treated with indomethacin (COX-1 and COX-2 inhibitor), celecoxib (COX-2 inhibitor), or placebo. SkBF was indexed as cutaneous vascular conductance (CVC), expressed as percentage of heat-induced maximal CVC (%MVC). Urinalyses were performed to test celecoxib treatment efficiency. No difference was found in CVC values at rest: 14.3 +/- 4.0, 11.9 +/- 3.2, and 10.9 +/- 2.0% MVC after indomethacin, celecoxib, and placebo treatment, respectively. At 10 min after the onset of anodal current application, CVC values were 22.2 +/- 4.9% MVC (not significantly different from rest) with indomethacin, 85.7 +/- 15.3% MVC (P < 0.001 vs. rest) with celecoxib, and 70.4 +/- 13.1% MVC (P < 0.001 vs. rest) with placebo. Celecoxib significantly depressed the urinary prostacyclin metabolite 6-keto-PGF(1alpha) (P < 0.05 vs. placebo). Indomethacin, but not celecoxib, significantly inhibited the anodal current-induced vasodilatation. Thus, although they are assumed to result from an axon reflex in primary afferent fibers and neurogenic inflammation, these results suggest that the early anodal current-induced vasodilatation is mainly dependent on COX-1-induced PG synthesis.
authors.affiliation: Laboratory of Vascular Investigations, University Hospital, University of Medicine, 49033 Angers Cedex, France.
authors.forename: Maylis
authors.initials: M
authors.lastname: Tartas
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouyé
authors.forename: Audrey
authors.initials: A
authors.lastname: Koïtka
authors.forename: Sylvain
authors.initials: S
authors.lastname: Durand
authors.forename: Yves
authors.initials: Y
authors.lastname: Gallois
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Saumet
authors.forename: Pierre
authors.initials: P
authors.lastname: Abraham
mesh_terms: D000328:Adult; D000068579:Celecoxib; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D004558:Electric Stimulation; D004566:Electrodes; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage*; D007478:Iontophoresis; D017078:Laser-Doppler Flowmetry; D008297:Male; D008565:Membrane Proteins; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011720:Pyrazoles / Q000008:administration & dosage; D012867:Skin / Q000098:blood supply; D013449:Sulfonamides / Q000008:administration & dosage; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; D007213:Indomethacin