Attenuated noradrenergic sensitivity during local cooling in aged human skin

Reflex-mediated cutaneous vasoconstriction (VC) is impaired in older humans; however, it is unclear whether this blunted VC also occurs during local cooling, which mediates VC through different mechanisms. We tested the hypothesis that the sensitization of cutaneous vessels to noradrenaline (NA) during direct skin cooling seen in young skin is blunted in aged skin. In 11 young (18-30 years) and 11 older (62-76 years) men and women, skin blood flow was monitored at two forearm sites with laser Doppler (LD) flowmetry while local skin temperature was cooled and clamped at 24 degrees C. Cutaneous vascular conductance (CVC; LD flux/mean arterial pressure) was expressed as percentage change from baseline (% Delta CVCbase). At one site, five doses of NA (10(-10)-10(-2) M) were sequentially infused via intradermal microdialysis during cooling while the other 24 degrees C site served as control (Ringer solution + cooling). At control sites, VC due to cooling alone was similar in young versus older (-54 +/- 5 versus -56 +/- 3% Delta CVCbase, P = 0.46). In young, NA infusions induced additional dose-dependent VC (10(-8), 10(-6), 10(-4) and 10(-2) M: -70 +/- 2, -72 +/- 3, -78 +/- 3 and -79 +/- 4% Delta CVCbase, P < 0.05 versus control). In older subjects, further VC did not occur until the highest infused dose of NA (10(-2) M: -70 +/- 5% Delta CVCbase; P < 0.05 versus control). When cutaneous arterioles are sensitized to NA by direct cooling, young skin exhibits the capacity to further constrict to NA in a dose-dependent manner. However, older skin does not display enhanced VC capacity until treated with saturating doses of NA, possibly due to age-associated decrements in Ca2+ availability or alpha(2c)-adrenoceptor function.