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

Abstract

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 (%DeltaCVC(base)). In protocol 1, two forearm skin sites were cooled to six temperatures (31.5-19 degrees C) for 10 min each or two temperatures (29 degrees C, 24 degrees 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 degrees 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.