Biomolecules & Therapeutics  
Hypothermia Inhibits Endothelium-Independent Vascular Contractility via Rho-kinase Inhibition
Yoon Hee Chung1,†, Keon Woong Oh2,†, Sung Tae Kim3, Eon Sub Park2, Hyun Dong Je4, Hyuk-Jun Yoon4, Uy Dong Sohn5, Ji Hoon Jeong3,* and Hyen-Oh La6,*
Departments of 1Anatomy, 2Pathology, 3Pharmacology, College of Medicine, Chung-Ang University, Seoul 06974,
4Department of Pharmacology, College of Pharmacy, Catholic University of Daegu, Gyeongsan 38430,
5Department of Pharmacology, College of Pharmacy, Chung Ang University, Seoul 06974,
6Department of Pharmacology, College of Pharmacy, The Catholic University of Korea, Bucheon 14662, Republic of Korea
E-mail: jhjeong3@cau.ac.kr (Jeong JH), hola@catholic.ac.kr (La HO)
Tel: +82-2-820-5688 (Jeong JH), +82-2-2164-4049 (La HO)
Fax: +82-2-826-8752 (Jeong JH), +82-2-2164-4059 (La HO)
The first two authors contributed equally to this work.
Received: October 20, 2016; Revised: December 11, 2016; Accepted: December 27, 2016; Published online: February 17, 2017.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
The present study was undertaken to investigate the influence of hypothermia on endothelium-independent vascular smooth muscle contractility and to determine the mechanism underlying the relaxation. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Hypothermia significantly inhibited fluoride-, thromboxane A2-, phenylephrine-, and phorbol ester-induced vascular contractions regardless of endothelial nitric oxide synthesis, suggesting that another pathway had a direct effect on vascular smooth muscle. Hypothermia significantly inhibited the fluoride-induced increase in pMYPT1 level and phorbol ester-induced increase in pERK1/2 level, suggesting inhibition of Rho-kinase and MEK activity and subsequent phosphorylation of MYPT1 and ERK1/2. These results suggest that the relaxing effect of moderate hypothermia on agonist-induced vascular contraction regardless of endothelial function involves inhibition of Rho-kinase and MEK activities.
Keywords: ERK1/2, fluoride, hypothermia, MYPT1, phorbol ester, Rho-kinase


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