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Cardiovascular Aging

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

¹Noll Laboratory, Department of Kinesiology, ²Graduate Program in Physiology, The Pennsylvania State University, University Park, Pennsylvania; ³Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland

Submitted 8 February 2007 ; accepted in final form 30 March 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 (%CVC_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.

fasudil; local cooling; vascular function; adrenergic; aging; cutaneous vasoconstriction