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Am J Physiol Heart Circ Physiol (April 6, 2007). doi:10.1152/ajpheart.00152.2007
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Submitted on February 8, 2007
Accepted on March 30, 2007

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

Caitlin S. Thompson-Torgerson1*, Lacy A. Holowatz2, Nicholas A. Flavahan1, and W. Larry Kenney3

1 Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
2 Kinesiology, Penn State, University Park, Pennsylvania, United States
3 Kinesiology Department, Pennsylvania State University, 102 Noll Lab, University Park, Pennsylvania, 16802-6900, United States; Graduate Program in Physiology, Pennsylvania State University, United States

* To whom correspondence should be addressed. E-mail: cthomp44{at}jhmi.edu.

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 7 young and 7 older subjects. Cutaneous vascular conductance (CVC; LDF/mean arterial pressure) was expressed as percentage change from baseline (%{Delta}CVCbase). Protocol 1: Two forearm skin sites were cooled to six temperatures (31.5-19°C) for 10 minutes each or two temperatures (29°C, 24°C) for 30 minutes each, with no age differences in the magnitude of VC. Protocol 2: Three forearm skin sites were instrumented for intradermal microdialysis and cooled to 24°C for 40 minutes. 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+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+adrenoceptor antagonism blocked more VC in older compared to 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.




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