Superoxide Inhibition Restores Endothelium-Dependent Dilatation in Aging Arteries by Enhancing Impaired Adherens Junctions

Endothelium-dependent, nitric oxide (NO)-mediated dilatation is impaired in aging arteries. The dysfunction reflects increased production of reactive oxygen species (ROS), is reversed by inhibiting superoxide with superoxide dismutase (SOD) mimics, and is assumed to reflect superoxide-mediated inactivation of NO. However, the dysfunction also reflects Src-dependent degradation and loss of VE-cadherin from adherens junctions, resulting in a selective impairment in the ability of the junctions to amplify endothelial dilatation. Experiments therefore tested the hypothesis that SOD mimics might restore endothelial dilation in aging arteries by inhibiting Src and protecting endothelial adherens junctions. Tail arteries from young and aging F344 rats were processed for functional (pressure myograph), biochemical (immunoblot) and morphological (immunofluorescence) analyses. Cell-permeable SOD mimics (MnTMPyP, Tempol) did not affect acetylcholine-induced dilatation in young arteries, but increased responses and r...