Rho kinase mediates cold-induced constriction of cutaneous arteries: Role of α2C-adrenoceptor translocation

S. R. Bailey, A. H. Eid, S. Mitra, S. Flavahan, Nicholas A. Flavahan

Research output: Contribution to journalArticlepeer-review

Abstract

Cold-induced vasoconstriction in cutaneous blood vessels is mediated in part by increased activity of vascular smooth muscle α2-adrenoceptors (VSM α2-ARs). In mouse cutaneous arteries, α2C-ARs are normally silent at 37°C but mediate cold-induced augmentation of α2-AR responsiveness. In transfected HEK293 cells, this functional rescue is mediated by cold-induced translocation of α2C-ARs from the Golgi to the plasma membrane. Experiments were performed to determine the role of Rho/Rho kinase signaling in this process. Inhibition of Rho kinase (fasudil, Y27632 or H-1152) did not affect constriction of isolated mouse tail arteries to the α2-AR agonist UK 14 304 at 37°C but dramatically reduced the augmented responses to the agonist at 28°C. After Rho kinase inhibition, cooling no longer increased constriction evoked by α2-AR stimulation. Cooling (to 28°C) activated Rho in VSM cells and increased the calcium sensitivity of constriction in a toxin-permeabilized arteries. Stimulation of α2-ARs in VSM cells had no effect on Rho activity or calcium sensitivity at 37°C or 28°C. In HEK293 cells transfected with α2C-ARs, cooling (to 28°C) stimulated the translocation of α2C-ARs to the plasma membrane and this effect was prevented by inhibition of Rho kinase, using fasudil or RNA interference. Consistent with inhibition of the spatial rescue of α2C-ARs, fasudil inhibited α2-AR-mediated mobilization of calcium in tail arteries at 28°C but not 37°C. Therefore, cold-induced activation of Rho/Rho kinase can mediate cold-induced constriction in cutaneous arteries by enabling translocation of α2C-ARs to the plasma membrane and by increasing the calcium sensitivity of the contractile process.

Original languageEnglish (US)
Pages (from-to)1367-1374
Number of pages8
JournalCirculation research
Volume94
Issue number10
DOIs
StatePublished - May 28 2004
Externally publishedYes

Keywords

  • HEK293 cells
  • Raynaud phenomenon
  • Thermoregulation
  • siRNA

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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