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

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

Research output: Contribution to journalArticlepeer-review

155 Scopus citations


Cold constricts cutaneous blood vessels by selectively increasing the activity of smooth muscle α2-adrenoceptors (α 2-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/1), 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/1) 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.

Original languageEnglish (US)
Pages (from-to)H243-H250
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number1 58-1
StatePublished - Jul 2005
Externally publishedYes


  • Mouse tail artery
  • Raynaud's phenomenon
  • Thermoregulation
  • α-adrenoceptors

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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