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

Kim, H, Seok, Y, Woodman, O, Williams, S and Kim, I 2012, '3 ',4 '-Dihydroxyflavonol reduces vascular contraction through Ca2+ desensitization in permeabilized rat mesenteric artery', Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 385, no. 2, pp. 191-202.


Document type: Journal Article
Collection: Journal Articles

Title 3 ',4 '-Dihydroxyflavonol reduces vascular contraction through Ca2+ desensitization in permeabilized rat mesenteric artery
Author(s) Kim, H
Seok, Y
Woodman, O
Williams, S
Kim, I
Year 2012
Journal name Naunyn-Schmiedeberg's Archives of Pharmacology
Volume number 385
Issue number 2
Start page 191
End page 202
Total pages 12
Publisher Springer
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 beta-escin and subjected to tension measurement. Cumulative addition of phenylephrine (0.3-30 mu M) produced concentration-dependent vascular contraction of endothelium-intact and endothelium-denuded arterial rings, which were inhibited by pretreatment with DiOHF (10, 30, or 100 mu M). In addition, DiOHF dose-dependently decreased vascular contractions induced by 3.0 mu M phenylephrine. beta-Escin-permeabilized third-order branches of mesenteric arteries were contracted with Ca2+, NaF, or guanosine-5'-(gamma-thio)triphosphate (GTP gamma S) 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 mu M GTP gamma S 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.
Subject Basic Pharmacology
Keyword(s) Dihydroxyflavonol (DiOHF)
Ca 2+ desensitization
GTP gamma S
NaF
permeabilized mesenteric artery
vascular contraction
DOI - identifier 10.1007/s00210-011-0697-8
Copyright notice © 2011 Springer-Verlag
ISSN 0028-1298
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