NYMC Faculty Publications

Hydrogen Peroxide Elicits Constriction of Skeletal Muscle Arterioles by Activating the Arachidonic Acid Pathway

Author Type(s)

Faculty

DOI

10.1371/journal.pone.0103858

Journal Title

PLoS One

First Page

103858

Last Page

103858

Document Type

Article

Publication Date

1-1-2014

Department

Physiology

Keywords

Animals, Arachidonic Acid, Arterioles, Coronary Vessels, Endothelium, Vascular, Heart, Hydrogen Peroxide, Male, Metabolic Networks and Pathways, Muscle, Skeletal, Rats, Rats, Wistar, Vasoconstriction

Disciplines

Medicine and Health Sciences

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. 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.

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