Cold-induced cutaneous vasoconstriction is mediated by Rho kinase in vivo in human skin

Cutaneous vasoconstriction ( VC) is the initial thermoregulatory response to cold exposure and can be elicited through either whole body or localized skin cooling. However, the mechanisms governing local cold-induced VC are not well understood. We tested the hypothesis that Rho kinase participates in local cold-induced cutaneous VC. In seven men and women ( 20 - 27 yr of age), up to four ventral forearm skin sites were instrumented with intradermal microdialysis fibers for localized drug delivery during cooling. Skin blood flow was monitored at each site with laser-Doppler flowmetry while local skin temperature was decreased and maintained at 24 degrees C for 40 min. Cutaneous vascular conductance ( CVC; laser-Doppler flowmetry/mean arterial pressure) was expressed as percent change from 34 degrees C baseline. During the first 5 min of cooling, CVC decreased at control sites ( lactated Ringer solution) to - 45 +/- 6% ( P < 0.001), increased at adrenoceptor-antagonized sites ( yohimbine + propranolol) to 15 +/- 14% ( P = 0.002), and remained unchanged at both Rho kinase-inhibited ( fasudil) and adrenoceptor-antagonized + Rho kinase-inhibited sites ( yohimbine + propranolol + fasudil) ( - 9 +/- 1%, P = 0.4 and - 6 +/- 2%, P = 0.4, respectively). During the last 5 min of cooling, CVC further decreased at all sites when compared with baseline values ( control, - 77 +/- 4%, P < 0.001; adrenoceptor antagonized, - 61 +/- 3%, P < 0.001; Rho kinase inhibited, - 34 +/- 7%, P < 0.001; and adrenoceptor antagonized + Rho kinase inhibited sites, - 35 +/- 3%, P < 0.001). Rho kinase-inhibited and combined treatment sites were significantly attenuated when compared with both adrenoceptor-antagonized ( P < 0.01) and control sites ( P < 0.0001). Rho kinase mediates both early- and late-phase cold-induced VC, supporting in vitro findings and providing a putative mechanism through which both adrenergic and nonadrenergic cold-induced VC occurs in an in vivo human thermoregulatory model.