Blockade of Urotensin II Receptor Prevents Vascular Dysfunction
Biomolecules & Therapeutics
;
: 523-528, 2016.
Article
Dans Anglais
| WPRIM
| ID: wpr-201377
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.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Aorte
/
Phosphorylation
/
Vasoconstriction
/
Artères carotides
/
Prolifération cellulaire
/
Néointima
/
Ligature
/
Muscles lisses
/
Muscles lisses vasculaires
Limites du sujet:
Animaux
/
Humains
langue:
Anglais
Texte intégral:
Biomolecules & Therapeutics
Année:
2016
Type:
Article
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