Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Vasorelaxing Effect of Hypoxia via Rho-kinase Inhibition on the Agonist-specific Vasoconstriction

  • Je, Hyun-Dong (Department of Pharmacology, College of Pharmacy, Catholic University of Daegu) ;
  • Shin, Chang-Yell (Korea and Research Laboratory, Dong-A Pharm. Co. Ltd.)
  • Published : 2008.09.30
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Abstract

The present study was undertaken to determine whether hypoxia influences on the agonist-induced vascular smooth muscle contraction and, if so, to investigate the related mechanism. The measurement of isometric contractions using a computerized data acquisition system was combined with molecular experiments. Hypoxia significantly inhibited fluoride-induced contraction regardless of endothelial function, but there was no relaxation on thromboxane $A_2$ mimetic U-46619-induced contraction suggesting that other pathway such as $Ca^{2+}$ entry or thin filament regulation was not affected. In addition, hypoxia significantly decreased fluoride-induced increase of phospho-myosin-targeting subunit of myosin light chain phosphatase (pMYPT1). Interestingly, hypoxia didn't inhibit significantly phenylephrine-induced contraction suggesting that myosin light chain kinase (MLCK) activity or thin filament regulation is less important on the hypoxia-induced vasorelaxation in the denuded muscle than Rho-kinase activity. In conclusion, this study provides the evidence and possible related mechanism concerning the vasodilation effect of hypoxia on the agonist-specific contraction in rat aortic rings regardless of endothelial function.

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References

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