Modulation of cutaneous vasodilation by reactive oxygen species during local and whole body heating in young and older adults

We evaluated reactive oxygen species (ROS) modulation of cutaneous vasodilation during local and whole body passive heating in young and older adults. Cutaneous vascular conductance normalized to maximum vasodilation (%CVC_max) was assessed in young and older adults (10/group) using laser-Doppler flowmetry at four dorsal forearm sites treated with <i>1</i>) Ringer solution (control), <i>2</i>) 100 µM apocynin (NADPH oxidase inhibitor), <i>3</i>) 10 µM allopurinol (xanthine oxidase inhibitor), or <i>4</i>) 10 µM tempol (superoxide dismutase mimetic), via intradermal microdialysis during local (<i>protocol 1</i>) and whole body heating (<i>protocol 2</i>). In <i>protocol 1</i>, forearm skin sites were set at 33°C during baseline and then progressively increased to 39°C and 42°C (30 min each). In <i>protocol 2</i>, participants were immersed in warm water (35°C, midsternum) with the experimental forearm above water level, and local skin sites were maintained at 34°C. Bath temperature was increased (∼40°C) to clamp core temperature at 38.5°C for 60 min. In <i>protocol 1</i>, there were significant treatment site by age interactions for the 39°C (<i>P</i> = 0.015) and 42°C (<i>P</i> = 0.004) plateaus; however no significant effects were observed after post hoc adjustment. In <i>protocol</i> 2, there was a significant treatment site by age interaction (<i>P</i> < 0.001), where %CVC_max in older adults was 11.0% [7.4, 14.6] higher for apocynin (<i>P</i> < 0.001), 8.9% [5.3, 12.5] higher for allopurinol (<i>P</i> < 0.001), and 4.8% [1.3, 8.4] higher for tempol (<i>P</i> = 0.016) sites relative to the control site. ROS derived from NADPH oxidase and xanthine oxidase attenuate cutaneous vasodilation in older adults during passive whole body heating, but not during local skin heating, with negligible effects on their young counterparts for either heating modality.<b>NEW & NOTEWORTHY</b> We found that local infusion of apocynin or allopurinol improved cutaneous vasodilator responses to passive whole body heating (but not local skin heating) in healthy older adults. These findings indicate that impaired microvascular responses to whole body heating with primary aging are linked to augmented production of reactive oxygen species (ROS) from NADPH oxidase and xanthine oxidase. This study sheds new light on the specific ROS pathways that modulate age-related changes in cutaneous microvascular responses to heating.