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HMC05 attenuates vascular contraction through inhibition of RhoA/Rho-kinase signaling pathway

Author:
Seok, Young Mi, Jin, Fanxue, Shin, Heung-Mook, Sung, Sang Hyun, Sohn, Uy Dong, Cho, Joon Yong, Kim, In Kyeom
Source:
Journal of ethnopharmacology 2011 v.133 no.2 pp. 484-489
ISSN:
0378-8741
Subject:
agonists, cardiovascular diseases, disease prevention, endothelium, guanosine triphosphate, myosin light chains, phenylephrine, phosphorylation, protein kinase C, rats, sodium fluoride
Abstract:
AIM OF THE STUDY: HMC05, an extract from eight different herbal mixtures, has been developed to treat cardiovascular disease. This extract has a vasorelaxant and anti-atherosclerotic action. We hypothesized that HMC05 attenuates vascular contraction through inhibition of the RhoA/Rho-kinase signaling pathway. MATERIALS AND METHODS: Rat aortic ring preparations were mounted in organ baths and subjected to contraction and relaxation. Phosphorylation of 20kDa myosin light chains (MLC₂₀) and myosin phosphatase targeting subunit 1 (MYPT1) were examined by immunoblot. We also measured the amount of GTP RhoA as a marker for RhoA activation. RESULTS: In endothelium-denuded aortic ring preparations, HMC05 relaxed vascular contraction induced by 6.0mM NaF, 100nM phenylephrine, 30nM thromboxane A₂ agonist U46619 or 1.0μM protein kinase C (PKC) activator phorbol-12,13-dibutyrate (PDBu) in a decreasing order. HMC05 relaxed aortic ring preparations precontracted with sodium fluoride (NaF) whether endothelium was intact or denuded. Pre-incubation with HMC05 for 30min dose-dependently inhibited the NaF-induced contractile response. In vascular strips, HMC05 decreased the phosphorylation level of both MLC₂₀ and MYPT1Tₕᵣ₈₅₅ induced by 6.0mM NaF. Furthermore, HMC05 decreased the amount of GTP RhoA activated by NaF. CONCLUSIONS: HMC05 attenuates vascular contraction through inhibition of the RhoA/Rho-kinase signaling pathway. HMC05 may be useful for the treatment and/or prevention of cardiovascular diseases associated with activation of RhoA/Rho-kinase signaling pathway.
Agid:
518000