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°C for 40 min. Cutaneous vascular conductance (CVC; laser-Doppler flowmetry/mean arterial pressure) was expressed as percent change from 34°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 earlyand 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.
|Original language||English (US)|
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|State||Published - Apr 1 2007|
All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine
- Physiology (medical)