TY - JOUR
T1 - Rho kinase mediates cold-induced constriction of cutaneous arteries
T2 - Role of α2C-adrenoceptor translocation
AU - Bailey, S. R.
AU - Eid, A. H.
AU - Mitra, S.
AU - Flavahan, S.
AU - Flavahan, Nicholas A.
PY - 2004/5/28
Y1 - 2004/5/28
N2 - 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.
AB - 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.
KW - HEK293 cells
KW - Raynaud phenomenon
KW - Thermoregulation
KW - siRNA
UR - http://www.scopus.com/inward/record.url?scp=2642569161&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=2642569161&partnerID=8YFLogxK
U2 - 10.1161/01.RES.0000128407.45014.58
DO - 10.1161/01.RES.0000128407.45014.58
M3 - Article
C2 - 15087420
AN - SCOPUS:2642569161
SN - 0009-7330
VL - 94
SP - 1367
EP - 1374
JO - Circulation research
JF - Circulation research
IS - 10
ER -