CALL FOR PAPERS Cardiovascular Aging Rho kinase-mediated local cold-induced cutaneous vasoconstriction is augmented in aged human skin

Thompson-Torgerson CS, Holowatz LA, Flavahan NA, Kenney WL. Rho kinase-mediated local cold-induced cutaneous vasoconstriction is augmented in aged human skin. Am J Physiol Heart Circ Physiol 293: H30–H36, 2007. First published April 6, 2007; doi:10.1152/ajpheart.00152.2007.—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 (% CVCbase). 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.