Biomol Ther.  2018 Mar;26(2):139-145. 10.4062/biomolther.2016.233.

Hypothermia Inhibits Endothelium-Independent Vascular Contractility via Rho-kinase Inhibition

Affiliations
  • 1Department of Anatomy, College of Medicine, Chung-Ang University, Seoul 06974, Republic of Korea.
  • 2Department of Pathology, College of Medicine, Chung-Ang University, Seoul 06974, Republic of Korea.
  • 3Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 06974, Republic of Korea.
  • 4Department of Pharmacology, College of Pharmacy, Catholic University of Daegu, Gyeongsan 38430, Republic of Korea.
  • 5Department of Pharmacology, College of Pharmacy, Chung Ang University, Seoul 06974, Republic of Korea.
  • 6Department of Pharmacology, College of Pharmacy, The Catholic University of Korea, Bucheon 14662, Republic of Korea. jhjeong3@cau.ac.kr

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.

Keyword

ERK1/2; fluoride; hypothermia; MYPT1; phorbol ester; Rho-kinase

MeSH Terms

Animals
Fluorides
Humans
Hypothermia*
Isometric Contraction
Male
Muscle, Smooth, Vascular
Nitric Oxide
Phosphorylation
Rats
Relaxation
rho-Associated Kinases*
Fluorides
Nitric Oxide
rho-Associated Kinases
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