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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 385, Issue 2, pp 191–202 | Cite as

3′,4′-Dihydroxyflavonol reduces vascular contraction through Ca2+ desensitization in permeabilized rat mesenteric artery

  • Hye Young Kim
  • Young Mi Seok
  • Owen L. Woodman
  • Spencer J. Williams
  • In Kyeom KimEmail author
ORIGINAL ARTICLE

Abstract

3′,4′-Dihydroxyflavonol (DiOHF) exerts endothelium-independent relaxation in rat aortic rings. In this study, we hypothesized that DiOHF reduces vascular contraction through Ca2+ desensitization in permeabilized third-order branches of rat mesenteric arteries. The third-order branches of rat mesenteric arteries were permeabilized with β-escin and subjected to tension measurement. Cumulative addition of phenylephrine (0.3–30 μM) produced concentration-dependent vascular contraction of endothelium-intact and endothelium-denuded arterial rings, which were inhibited by pretreatment with DiOHF (10, 30, or 100 μM). In addition, DiOHF dose-dependently decreased vascular contractions induced by 3.0 μM phenylephrine. β-Escin-permeabilized third-order branches of mesenteric arteries were contracted with Ca2+, NaF, or guanosine-5′-(γ-thio)triphosphate (GTPγS) 30 min after pretreatment with DiOHF or vehicle. Pretreatment with DiOHF for 30 min inhibited vascular contraction induced by cumulative additions of Ca2+ (pCa 9.0–6.0) or NaF (4.0–16.0 mM) in permeabilized arterial rings. Cumulative addition of DiOHF also reduced vascular contraction induced by Ca2+-controlled solution of pCa 6.0, 16.0 mM NaF, or 100 μM GTPγS in permeabilized arterial rings. DiOHF inhibited the increase in vascular tension provoked by calyculin A, even though it did not affect vascular tension already produced by calyculin A. DiOHF accelerated the relaxation induced by rapidly lowering Ca2+. DiOHF reduced vascular contraction through Ca2+ desensitization in permeabilized third-order branches of rat mesenteric arteries. These results suggest that DiOHF may have a therapeutic potential in the treatment of cardiovascular diseases.

Keywords

3′,4′-Dihydroxyflavonol (DiOHF) Ca2+ desensitization Permeabilized mesenteric artery β-escin Vascular contraction GTPγS NaF 

Abbreviation

AlF4

Aluminum tetrafluoride

[Ca2+]i

Intracellular free calcium concentration

CPI17

PKC-potentiated inhibitory protein for heterotrimeric MLCP of 17 kDa

DiOHF

3′,4′-Dihydroxyflavonol

EGTA

Ethylene glycol bis(2-aminoethyl ether)-N,N,NN′-tetraacetic acid

GPCRs

G protein-coupled receptors

GTP

Guanosine-5′-triphosphate

GTPγS

Guanosine-5′-(γ-thio)triphosphate

MLC

Myosin light chain

MLCK

Myosin light chain kinase

MLCP

Myosin light chain phosphatase

MYPT1

Myosin phosphatase targeting subunit 1

NaF

Sodium fluoride

pCa

−log [Ca2+]

PDBu

Phorbol 12,13-dibutyrate

PIPES

Piperazine-1,4-bis(2-ethanesulfonic acid)

PKC

Protein kinase C

SPC

Sphingosylphosphorylcholine

SR

Sarcoplasmic reticulum

Notes

Acknowledgments

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2011-0014066) and the Brain Korea 21 Project in 2011.

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Hye Young Kim
    • 1
  • Young Mi Seok
    • 2
  • Owen L. Woodman
    • 3
  • Spencer J. Williams
    • 4
  • In Kyeom Kim
    • 1
    • 2
    • 5
    Email author
  1. 1.Department of PharmacologyKyungpook National University School of MedicineDaeguRepublic of Korea
  2. 2.Cardiovascular Research InstituteKyungpook National University School of MedicineDaeguRepublic of Korea
  3. 3.School of Medical SciencesRMIT UniversityBundooraAustralia
  4. 4.School of Chemistry and Bio21 Molecular Science and Biotechnology InstituteUniversity of MelbourneParkvilleAustralia
  5. 5.Cell and Matrix Research InstituteKyungpook National University School of MedicineDaeguRepublic of Korea

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