Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Blockade of Urotensin II Receptor Prevents Vascular Dysfunction

  • Kim, Young-Ae (College of Pharmacy, Ajou University) ;
  • Lee, Dong Gil (College of Pharmacy, Ajou University) ;
  • Yi, Kyu Yang (Research Center for Drug Discovery Technology, Korea Research Institute of Chemical Technology) ;
  • Lee, Byung Ho (Research Center for Drug Discovery Technology, Korea Research Institute of Chemical Technology) ;
  • Jung, Yi-Sook (College of Pharmacy, Ajou University)
  • Received : 2015.09.04
  • Accepted : 2015.09.17
  • Published : 2016.09.01
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Abstract

Urotensin II (UII) is a potent vasoactive peptide and mitogenic agent to induce proliferation of various cells including vascular smooth muscle cells (VSMCs). In this study, we examined the effects of a novel UII receptor (UT) antagonist, KR-36676, on vasoconstriction of aorta and proliferation of aortic SMCs. In rat aorta, UII-induced vasoconstriction was significantly inhibited by KR-36676 in a concentration-dependent manner. In primary human aortic SMCs (hAoSMCs), UII-induced cell proliferation was significantly inhibited by KR-36676 in a concentration-dependent manner. In addition, KR-36676 decreased UII-induced phosphorylation of ERK, and UII-induced cell proliferation was also significantly inhibited by a known ERK inhibitor U0126. In mouse carotid ligation model, intimal thickening of carotid artery was dramatically suppressed by oral treatment with KR-36676 (30 mg/kg/day) for 4 weeks compared to vehicle-treated group. From these results, it is indicated that KR-36676 suppress UII-induced proliferation of VSMCs at least partially through inhibition of ERK activation, and that it also attenuates UII-induced vasoconstriction and vascular neointima formation. Our study suggest that KR-36676 may be an attractive candidate for the pharmacological management of vascular dysfunction.

Keywords

References

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