Reactive Oxygen Species Are Essential for Vasoconstriction upon Cold Exposure

Area of Science:

• Physiology
• Molecular Biology
• Vascular Biology

Background:

• Cold exposure can induce vasoconstriction, impacting blood flow.
• The precise mechanisms underlying cold-induced vasoconstriction, particularly the role of reactive oxygen species (ROS), require further elucidation.

Purpose of the Study:

• To investigate the role of ROS in cold-induced vasoconstriction.
• To identify the underlying molecular mechanisms involved in this vascular response.

Main Methods:

• Human hand blood flow was measured before and after cold exposure.
• Mice were treated with saline, subcutaneous, or intrathecal Tempol (a ROS scavenger) to assess its effect on cold-induced vasoconstriction.
• Human aortic vascular smooth muscle cells (HAVSMCs) and human umbilical vein endothelial cells (HUVECs) were pretreated with Tempol, CCG-1423, or Go 6983, then exposed to cold to analyze cellular changes, calcium levels, ROS production, and protein expression via various assays.

Main Results:

• Cold exposure reduced human hand blood flow.
• Subcutaneous Tempol administration increased skin blood flow post-cold exposure in mice.
• Cold exposure increased intracellular calcium and ROS levels, cell shrinkage, and altered expression of proteins involved in vasoconstriction (RhoA, Rock1, p-MLC-2, ET-1, iNOS, p-PKC) while decreasing eNOS expression.
• Tempol, CCG-1423, and Go 6983 treatments modulated these cellular and molecular changes, reducing ROS and calcium levels and affecting key protein expressions.

Conclusions:

• Reactive oxygen species (ROS) play a critical role in mediating vasoconstriction during cold exposure.
• The vasoconstrictor response to cold involves ROS acting within blood vessel tissues, specifically through the ROS/RhoA/ROCK1 and ROS/PKC/ET-1 pathways in vascular smooth muscle cells and endothelial cells, rather than through nerve fibers.