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


METHODS
Rat aortic ring preparations were mounted in organ baths and subjected to contraction and relaxation. Phosphorylation of 20 kDa myosin light chains (MLC(20)) 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 6.0 mM NaF, 100 nM phenylephrine, 30 nM thromboxane A(2) agonist U46619 or 1.0 μM 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 30 min dose-dependently inhibited the NaF-induced contractile response. In vascular strips, HMC05 decreased the phosphorylation level of both MLC(20) and MYPT1(Thr855) induced by 6.0 mM 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.
Department of Pharmacology, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
Young Mi
YM
Seok
Fanxue
F
Jin
Heung-Mook
HM
Shin
Sang Hyun
SH
Sung
Uy Dong
UD
Sohn
Joon Yong
JY
Cho
In Kyeom
IK
Kim
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002318:Cardiovascular Diseases / Q000188:drug therapy; D020834:Ethnopharmacology; D066298:In Vitro Techniques; D008297:Male; D055670:Medicine, Korean Traditional; D018994:Myosin Light Chains / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D054645:Protein Phosphatase 1 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D056910:Republic of Korea; D015398:Signal Transduction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
C526235:HMCO5 herbal extract; D018994:Myosin Light Chains; D010936:Plant Extracts; D014665:Vasodilator Agents; D054460:rho-Associated Kinases; C499850:Ppp1r12a protein, rat; D054645:Protein Phosphatase 1; D020742:rhoA GTP-Binding Protein