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(Circulation Research. 2004;94:1367.)
© 2004 American Heart Association, Inc.

Integrative Physiology

Rho Kinase Mediates Cold-Induced Constriction of Cutaneous Arteries

Role of 2C-Adrenoceptor Translocation

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

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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