Rho kinase-mediated local cold-induced cutaneous vasoconstriction is augmented in aged human skin

Cutaneous vasoconstriction (VC), a critical thermoregulatory response to cold, is generally impaired with aging. However, the effects of aging on local cooling-induced VC and its underlying mechanisms are poorly understood. We tested whether aged skin exhibits attenuated localized cold-induced VC and whether Rho kinase-mediated cold-induced VC is augmented with age. Skin blood flow was monitored with laser Doppler flowmetry (LDF) on seven young and seven older subjects. Cutaneous vascular conductance (CVC; LDF/mean arterial pressure) was expressed as percentage change from baseline (%ΔCVC_base). In protocol 1, two forearm skin sites were cooled to six temperatures (31.5-19°C) for 10 min each or two temperatures (29°C, 24°C) for 30 min each, with no age differences in the magnitude of VC. In protocol 2, three forearm skin sites were instrumented for intradermal microdialysis and cooled to 24°C for 40 min. During minutes 1-5, there was no age difference in CVC responses at control sites (young: -45 ± 6% vs. older: -46 ± 3%, P > 0.9). Adrenoceptor antagonism (yohimbine + propranolol) abolished VC in young (to +15 ± 13%, P < 0.05) but only partially inhibited VC in older subjects (to -23 ± 6%, P < 0.05). Rho kinase inhibition plus adrenoceptor antagonism (yohimbine + propranolol + fasudil) abolished VC in both groups. During minutes 35-40, there was no age difference in control (young: -77 ± 4% vs. older: -70 ± 2%, P > 0.3) or adrenoceptor- antagonized responses (young: -61 ± 3% vs. older: -55 ± 2%, P > 0.3); however, Rho kinase inhibition plus adrenoceptor antagonism blocked more VC in older compared with young subjects (-19 ± 11% vs. -35 ± 3%, P < 0.05). Although its magnitude remains unaffected, cold-induced VC becomes less dependent on adrenergic and more dependent on Rho kinase signaling with advancing age.