Flavone inhibits vascular contraction by decreasing phosphorylation of the myosin phosphatase target subunit.
1. Flavonoids modulate vascular tone through an endothelium-dependent or -independent mechanism. Although a few mechanisms for endothelium-independent relaxation have been suggested, such as interference with protein kinase C or cAMP or cGMP phosphodiesterase, the inhibition of Ca(2+) release from intracellular stores or Ca(2+) influx from extracellular fluids, the mode of action of flavonoids remains elusive. 2. We hypothesized that treatment with flavone inhibits vascular smooth muscle contraction by decreasing the phosphorylation of the myosin phosphatase target subunit (MYPT1). 3. Rat aortic rings were denuded of endothelium, mounted in organ baths and contracted with U46619, a thromboxane A(2) analogue. 4. Flavone dose-dependently inhibited the U46619-induced contractile response and myosin light chain (MLC(20)) phosphorylation. At 10(-7) mol/L, U46619 induced vascular contraction with the concomitant phosphorylation of MYPT1 at Thr855, but not at Thr697. Incubation with flavone (100 or 300 micromol/L) for 30 min attenuated the phosphorylation of MYPT1(Thr855), but not MYPT1(Thr697). 5. It is concluded that treatment with flavone inhibits vascular smooth muscle contraction by decreasing the phosphorylation of the MYPT1. These results suggest that flavone causes endothelium-independent relaxation through, at least in part, the inhibition of p160 Rho-associated coiled-coil-containing protein kinase (ROCK) signalling.
Jeon
Su Bun
SB
Department of Pharmacology, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
Kim
Gutae
G
Kim
Jee In
JI
Seok
Young Mi
YM
Kim
Sang-Hyun
SH
Suk
Kyoungho
K
Shin
Heung-Mook
HM
Lee
Young-Ho
YH
Kim
In Kyeom
IK
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D047309:Flavones; D005419:Flavonoids / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*; D054460:rho-Associated Kinases / Q000378:metabolism
D047309:Flavones; D005419:Flavonoids; D018994:Myosin Light Chains; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D054460:rho-Associated Kinases; C499850:Ppp1r12a protein, rat; D054645:Protein Phosphatase 1; C043562:flavone