title: Hydrogen peroxide elicits constriction of skeletal muscle arterioles by activating the arachidonic acid pathway.
abstract: OBJECTIVE
  The molecular mechanisms of the vasoconstrictor responses evoked by hydrogen peroxide (H2O2) have not been clearly elucidated in skeletal muscle arterioles.
  
  
  RESULTS
  Changes in diameter of isolated, cannulated and pressurized gracilis muscle arterioles (GAs) of Wistar-Kyoto rats were determined under various test conditions. H2O2 (10-100 µM) evoked concentration-dependent constrictions in the GAs, which were inhibited by endothelium removal, or by antagonists of phospholipase A (PLA; 100 µM 7,7-dimethyl-(5Z,8Z)-eicosadienoic acid), protein kinase C (PKC; 10 µM chelerythrine), phospholipase C (PLC; 10 µM U-73122), or Src family tyrosine kinase (Src kinase; 1 µM Src Inhibitor-1). Antagonists of thromboxane A2 (TXA2; 1 µM SQ-29548) or the non-specific cyclooxygenase (COX) inhibitor indomethacin (10 µM) converted constrictions to dilations. The COX-1 inhibitor (SC-560, 1 µM) demonstrated a greater reduction in constriction and conversion to dilation than that of COX-2 (celecoxib, 3 µM). H2O2 did not elicit significant changes in arteriolar Ca(2+) levels measured with Fura-2.
  
  
  CONCLUSIONS
  These data suggest that H2O2 activates the endothelial Src kinase/PLC/PKC/PLA pathway, ultimately leading to the synthesis and release of TXA2 by COX-1, thereby increasing the Ca(2+) sensitivity of the vascular smooth muscle cells and eliciting constriction in rat skeletal muscle arterioles.
authors.affiliation: Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary; Research Centre for Molecular Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Viktória
authors.initials: V
authors.lastname: Csató
authors.affiliation: Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary; Research Centre for Molecular Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Pető
authors.affiliation: Department of Pathophysiology and Gerontology, University of Pécs, Pécs, Hungary; Department of Pathophysiology, Semmelweis University, Budapest, Hungary; Department of Physiology, New York Medical College, Valhalla, New York, United States of America.
authors.forename: Ákos
authors.initials: Á
authors.lastname: Koller
authors.affiliation: Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary; Research Centre for Molecular Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Édes
authors.affiliation: Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary; Research Centre for Molecular Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Tóth
authors.affiliation: Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary; Research Centre for Molecular Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Papp
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D016718:Arachidonic Acid; D006861:Hydrogen Peroxide
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