Reactive oxygen species from smooth muscle mitochondria initiate cold-induced constriction of cutaneous arteries

American Journal of Physiology - Heart and Circulatory Physiology - Tập 289 Số 1 - Trang H243-H250 - 2005
Simon Bailey1, Sayan Mitra2, Sheila Flavahan2, Nicholas A. Flavahan2
1Davis Heart and Lung Research Institute, R 110E, The Ohio State Univ., 473 West 12th Ave, Columbus, OH 43210, USA.
2Ohio State University

Tóm tắt

Cold constricts cutaneous blood vessels by selectively increasing the activity of smooth muscle α2-adrenoceptors (α2-ARs). In mouse tail arteries, α2-AR constriction is mediated by α2A-ARs at 37°C, whereas the cold-induced augmentation in α2-AR activity is mediated entirely by α2C-ARs. Cold causes translocation of α2C-ARs from the trans-Golgi to the plasma membrane, mediated by cold-induced activation of RhoA and Rho kinase. The present experiments analyzed the mechanisms underlying these responses. Mouse tail arteries were studied in a pressure myograph. Cooling the arteries (28°C) caused a rapid increase in reactive oxygen species (ROS) in smooth muscle cells, determined by confocal microscopy of arteries loaded with the ROS-sensitive probes, dichlorodihydrofluorescein or reduced Mitotracker Red. The inhibitor of mitochondrial complex I rotenone (10 μmol/l), the antioxidant N-acetylcysteine (NAC; 20 mmol/l), or the cell-permeable mimic of superoxide dismutase MnTMPyP (50 μmol/l) did not affect vasoconstriction to α2-AR stimulation (UK-14304) at 37°C but dramatically inhibited the response at 28°C. Indeed, these ROS inhibitors abolished the cold-induced increase in α2-AR constrictor activity. NAC (20 mmol/l) or MnTMPyP (50 μmol/l) also abolished the cold-induced activation of RhoA in human cultured vascular smooth muscle cells and the cold-induced mobilization of α2C-ARs to the cell surface in human embryonic kidney 293 cells transfected with the receptor. The combined results suggest that cold-induced constriction is mediated by redox signaling in smooth muscle cells, initiated by mitochondrial generation of ROS, which stimulate RhoA/Rho kinase signaling and the subsequent mobilization of α2C-ARs to the cell surface. Altered activity of ROS may contribute to cold-induced vasospasm occurring in Raynaud's phenomenon.

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American Journal of Physiology - Heart and Circulatory Physiology

Tập 289 Số 1

H243-H250

Thông tin tác giả