Blockade of Urotensin II Receptor Prevents Vascular Dysfunction.
10.4062/biomolther.2015.142
- Author:
Young Ae KIM
1
;
Dong Gil LEE
;
Kyu Yang YI
;
Byung Ho LEE
;
Yi Sook JUNG
Author Information
1. College of Pharmacy, Ajou University, Suwon 16499, Republic of Korea. yisjung@ajou.ac.kr
- Publication Type:Original Article
- Keywords:
Urotensin II;
Urotensin II receptor antagonist;
KR-36676;
ERK;
Smooth muscle;
Proliferation
- MeSH:
Animals;
Aorta;
Carotid Arteries;
Cell Proliferation;
Humans;
Ligation;
Mice;
Muscle, Smooth;
Muscle, Smooth, Vascular;
Neointima;
Phosphorylation;
Rats;
Vasoconstriction
- From:Biomolecules & Therapeutics
2016;24(5):523-528
- CountryRepublic of Korea
- Language:English
-
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.
