Relative contributions of mitochondrial and non-mitochondrial oxidative stress in age-related cutaneous microvascular endothelial dysfunction.

Abstract

Aging is associated with oxidative-stress-induced endothelial dysfunction, characterized by reduced nitric oxide (NO) signaling. The present study evaluated the contributions of mitochondrial- and non-mitochondrial oxidative stress in age-related endothelial dysfunction. Three intradermal microdialysis fibers were placed in the forearm for local delivery of pharmacological agents (10mM Tempol, 1mM MitoTempo, Ringer's vehicle control) to the cutaneous microvasculature in fifteen older (67 ± 3 yrs; 7 M, 8 F) adults. After ~20 min baseline, local heating (42°C) induced cutaneous vasodilation, and perfusion of a NO synthase inhibitor (15mM L-NAME) allowed quantification of the NO- and non-NO contributions to the local heating response. Red cell flux was measured at each site by laser-Doppler flowmetry (LDF) and cutaneous vascular conductance (CVC=LDF/MAP) was expressed as a percentage of maximum (%CVC