Hydrogen peroxide elicits constriction of skeletal muscle arterioles by activating the arachidonic acid pathway

Viktória Csató, Attila Peto, Ákos Koller, István Édes, Attila Tóth, Zoltán Papp

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Aims: The molecular mechanisms of the vasoconstrictor responses evoked by hydrogen peroxide (H2O2) have not been clearly elucidated in skeletal muscle arterioles. Methods and Results: Changes in diameter of isolated, cannulated and pressurized gracilis muscle arterioles (GAs) of Wistar-Kyoto rats were determined under various test conditions. H 2O2 (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 Ca2+ 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.

Original languageEnglish
Article numbere103858
JournalPloS one
Volume9
Issue number8
DOIs
Publication statusPublished - Aug 5 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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