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Effects of 3′,4′‐dihydroxyflavonol on vascular contractions of rat aortic rings
Author(s) -
Song MinJi,
Baek Inji,
Seo Minchul,
Kim SangHyun,
Suk Kyoungho,
Woodman Owen L,
Williams Spencer J,
Kim InKyeom
Publication year - 2010
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2010.05384.x
Subject(s) - rhoa , myosin light chain phosphatase , vascular smooth muscle , myosin light chain kinase , apamin , chemistry , contraction (grammar) , glibenclamide , vasodilation , medicine , endocrinology , phosphorylation , anatomy , biology , potassium channel , biochemistry , signal transduction , smooth muscle , diabetes mellitus
Summary 1. 3′,4′‐Dihydroxyflavonol (DiOHF) is an effective vasodilator with anti‐oxidant activity. The aim of the present study was to elucidate the effects of DiOHF on vascular contractions. 2. Contractile and relaxation responses were determined in rat endothelium‐denuded aortic rings mounted in organ baths. In addition, the phosphorylation of myosin light chain (MLC 20 ), myosin phosphatase targeting subunit 1 (MYPT1) and protein kinase C (PKC)‐potentiated inhibitory protein for heterotrimeric myosin light chain phosphatase of 17 kDa (CPI‐17) was determined using western blot analaysis. Levels of GTP RhoA, as a marker of RhoA activation, were also measured. 3. Cumulative addition of increasing concentrations of NaF (3.0–12.0 mmol/L) or U46619 (1.0–1000 nmol/L) concentration‐dependently increased vascular tension. These responses were inhibited by pretreatment of aortic rings with DiOHF (10, 30 or 100 μmol/L), which dose‐dependently decreased vascular contractions induced by 8.0 mmol/L NaF, 30 nmol/L U46619, 0.1 μmol/L phenylephrine and 50 mmol/L KCl. 4. The K + channel blockers 4‐aminopyridine (3 mmol/L), charybdotoxin (10 nmol/L), apamin (500 nmol/L) and glibenclamide (10 μmol/L) had no effect on vascular relaxation induced by DiOHF (1–30 μmol/L). 5. At 30 μmol/L, DiOHF decreased the activation of RhoA and subsequent phosphorylation of MYPT1, CPI‐17 and MLC 20 to almost basal levels. 6. In conclusion, DiOHF decreases vascular contraction at least partly by inhibition of the RhoA/Rho‐kinase pathway in rat endothelium‐denuded aorta. These results suggest that DiOHF may have therapeutic potential in the treatment of cardiovascular diseases.