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Reactive Oxygen Species (ROS) from NADPH and Xanthine Oxidase Modulate the Cutaneous Local Heating Response in Chronic Fatigue Syndrome
Author(s) -
Medow Marvin Scott,
Aggarwal Arun,
Baugham Ila,
Messer Zachary,
Stewart Julian M.
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.678.10
Subject(s) - apocynin , xanthine oxidase , nadph oxidase , allopurinol , reactive oxygen species , chemistry , superoxide , medicine , endocrinology , xanthine oxidase inhibitor , pharmacology , biochemistry , enzyme
Local cutaneous heating causes vasodilation as an initial peak, a nadir, and increase to plateau. We showed reactive oxygen species (ROS) produced by Ang‐II via NADPH and xanthine oxidase, modulates this response in healthy controls. The initial peak, due to C‐fibre nociceptor‐mediated axon reflex and local release of calcitonin gene‐related peptide, substance P and neuropeptide Y, is blunted with local anesthetics. To determine the role of ROS in this neurovascular response, we studied orthostatically‐challenged, Chronic Fatigue Syndrome (CFS) subjects. We heated the skin of 9 CFS subjects (15.8–22.0 years) to 42°C and measured local blood flow. While CFS subjects had lower baseline blood flow (79% of control), there were no differences between groups to local heat. We then measured CFS subjects while perfusing apocynin (NADPH oxidase inhibitor), allopurinol (xanthine oxidase inhibitor), tempol (superoxide inhibitor), and ebselen to reduce H 2 O 2 via microdialysis catheters. Allopurinol and ebselen only enhanced the first heat peak (117% and 126% of heat‐alone, respectively). Heat with apocynin caused an increase in baseline (170% of non‐drug) and of the first heat peak (114% of heat‐alone). Tempol had no effect. Thus the response to heat, as indicated by the first peak, may be altered by local levels of ROS in CFS subjects, and may be related to hyperesthesia/hyperalgesia reported by many individuals with CFS. Supported by the National Heart, Lung, and Blood Institute Grants 1‐RO1‐HL‐074873, 1‐RO1‐HL‐087803 and 1‐F30‐HL‐097380 and a grant from the Chronic Fatigue and Immune Dysfunction Syndrome Association.