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Rho kinase activation and ROS production contributes to the cooling enhanced contraction in cutaneous equine digital
H Zerpa1, Y Berhane, H Woodcock
1Department of Veterinary Basic Sciences, Royal Veterinary College, University of London, London, United Kingdom.
Journal of Applied Physiology (Bethesda, Md. : 1985)
|April 3, 2010
Summary
Cooling enhances equine digital vein contraction via alpha(2)-adrenoceptor agonists, primarily through Rho kinase activation and reactive oxygen species (ROS) production. Protein kinase C also plays a role at warmer temperatures.
Area of Science:
- Physiology
- Pharmacology
- Vascular Biology
Background:
- Environmental temperature influences cutaneous vasculature contractility, partly mediated by alpha(2)-adrenoceptors.
- While mechanisms in cutaneous arteries are known, less is understood about cutaneous veins.
Purpose of the Study:
- To investigate the cellular mechanisms of cooling-enhanced contraction to an alpha(2)-adrenoceptor agonist in isolated equine digital veins (EDVs).
Main Methods:
- Isolated EDVs were studied at 30°C and 22°C, assessing contractile responses to UK-14304 (an alpha(2)-adrenoceptor agonist).
- The effects of Rho kinase inhibitors (fasudil, Y-27632), protein kinase C inhibitor (chelerythrine), and antioxidants (rotenone, tempol) were evaluated.
- Western blotting assessed the phosphorylation of ezrin/radixin/moesin.
Main Results:
- Cooling significantly enhanced UK-14304-induced contraction, an effect largely inhibited by Rho kinase inhibitors at 22°C but less so at 30°C.
- Rho kinase activity, indicated by ezrin/radixin/moesin phosphorylation, increased upon cooling and was reduced by fasudil at 22°C.
- Protein kinase C contributed to contraction mainly at 30°C, while reactive oxygen species (ROS) were implicated in the cooling-enhanced response at 22°C.
Conclusions:
- Rho kinase activation and ROS production are key mechanisms underlying cooling-enhanced contraction in equine digital veins.
- Protein kinase C activation is temperature-dependent, contributing more significantly at warmer temperatures.
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