title: Cold-induced cutaneous vasoconstriction is mediated by Rho kinase in vivo in human skin.
abstract: 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.
authors.affiliation: Noll Laboratory, Department of Kinesiology, The Pennsylvania State University, University Park, Pennsylvania 21205, USA. cthomp44@jhmi.edu
authors.forename: Caitlin S
authors.initials: CS
authors.lastname: Thompson-Torgerson
authors.forename: Lacy A
authors.initials: LA
authors.lastname: Holowatz
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Flavahan
authors.forename: W Larry
authors.initials: WL
authors.lastname: Kenney
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000328:Adult; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology*; D003080:Cold Temperature; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017078:Laser-Doppler Flowmetry; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage; D011433:Propranolol / Q000008:administration & dosage; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012867:Skin / Q000098:blood supply / Q000201:enzymology*; D012881:Skin Temperature / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage; D015016:Yohimbine / Q000008:administration & dosage; D054460:rho-Associated Kinases
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D014662:Vasoconstrictor Agents; D015016:Yohimbine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011433:Propranolol; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; C049347:fasudil; D009638:Norepinephrine