Hydrogen Peroxide Emerges as a Regulator of Tone in Skeletal Muscle Arterioles During Juvenile Growth

Abstract

Objective: The endothelium-dependent dilation of skeletal muscle arterioles is mediated by factors that have not been identified in young rats, and partly mediated by an unidentified hyperpolarizing factor in maturing rats. This study was designed to determine if endogenous hydrogen peroxide (H₂O₂) contributes to this arteriolar dilation at either of these growth stages.

Methods: Gracilis muscle arterioles were isolated from rats at ages 24–26 days (“weanlings”) and 46–48 days (“juveniles”). We investigated the effects of catalase treatment on the endothelium-dependent dilation of these vessels to simvastatin and acetylcholine (ACh). Catalase-sensitive 2′,7′-dichlorofluorescein (DCF) fluorescence also was measured as an index of H₂O₂ formation, and arteriolar dilation to exogenous H₂O₂ was pharmacologically probed in each age group.

Results: Responses to simvastatin and ACh were attenuated by catalase in juvenile, but not weanling, arterioles. Juvenile, but not weanling, arterioles also displayed catalase-sensitive DCF fluorescence that was increased by ACh. Exogenous H₂O₂ could induce dilation in juvenile, but not weanling, arterioles. In juvenile arterioles, this dilation was abolished by the K⁺ channel inhibitors TEA and glibenclamide, and attenuated by NOS inhibition or endothelial removal.

Conclusions: These findings suggest that endogenous H₂O₂ contributes to endothelium-dependent arteriolar dilation in juvenile rats, but not in younger rats, and that H₂O₂ acts in juvenile rats by stimulating endothelial NO release and activating smooth muscle K⁺ channels.

Key words:

• arterioles
• endothelium
• postnatal growth
• hydrogen peroxide

ACKNOWLEDGMENTS

This work was funded by the American Heart Association (grant nos. 0330194N to JCF and 0150199N to MAB) and the National Institutes of Health (grant nos. R01 DK64668 to JCF NIH and RO1 HL44012 to MAB).