Published online before print April 15, 2004, doi: 10.1161/01.RES.0000128407.45014.58
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© 2004 American Heart Association, Inc.
Integrative Physiology |
Rho Kinase Mediates Cold-Induced Constriction of Cutaneous Arteries
Role of 
2C-Adrenoceptor Translocation
From the Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus.
Correspondence to Nicholas A. Flavahan, Heart and Lung Research Institute, R 110E, The Ohio State University, 473 West 12th Ave, Columbus, OH 43210. E-mail flavahan-1{at}medctr.osu.edu
Cold-induced vasoconstriction in cutaneous blood vessels is mediated in part by increased activity of vascular smooth muscle 2-adrenoceptors (VSM 2-ARs). In mouse cutaneous arteries, 2C-ARs are normally silent at 37°C but mediate cold-induced augmentation of 2-AR responsiveness. In transfected HEK293 cells, this functional rescue is mediated by cold-induced translocation of 2C-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 2-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 2-AR stimulation. Cooling (to 28°C) activated Rho in VSM cells and increased the calcium sensitivity of constriction in toxin-permeabilized arteries. Stimulation of 2-ARs in VSM cells had no effect on Rho activity or calcium sensitivity at 37°C or 28°C. In HEK293 cells transfected with 2C-ARs, cooling (to 28°C) stimulated the translocation of 2C-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 2C-ARs, fasudil inhibited 2-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 2C-ARs to the plasma membrane and by increasing the calcium sensitivity of the contractile process.
Key Words: raynaud phenomenon • siRNA • thermoregulation • HEK293 cells
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