Formononetin, an isoflavone, relaxes rat isolated aorta through endothelium-dependent and endothelium-independent pathways
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AbstractWe evaluated the vasorelaxation effects of formononetin, an isoflavone/phytoestrogen found abundantly in Astragalus mongholicus Bunge, on rat isolated aorta and the underlying mechanisms involved. Cumulative administration of formononetin, genistein. daidzein and biochanin A relaxed phenylephrine-preconstricted aorta. Formononetin and biochanin A caused a similar magnitude of relaxation whereas daidzein was least potent. Mechanical removal of endothelium, L-NAME (100 mu M) and methylene blue (10 mu M) suppressed formononetin-induced relaxation. Formononetin increased endothelial nitric oxide (NO) synthase (eNOS), but not inducible NO synthase, activity with an up-regulation of eNOS mRNA and p-eNOS(ser1177) protein expression. In endothelium-denuded preparations, formononetin-induced vasorelaxation was significantly reduced by glibenclamide (3 mu M) and iberiotoxin (100 nM), and a combination of glibenclamide (3 mu M) plus iberiotoxin (100 nM) abolished the relaxation. In contrast, formononetin-elicited endothelium-independent relaxation was not altered by ICI 182,780 (10 mu M, an estrogen receptor (ER alpha/ER beta) antagonist) or mifepristone (10 mu M, a progesterone receptor antagonist). In single aortic smooth muscle cells, formononetin caused opening of iberiotoxin-sensitive Ca2+-activated K+ (BKCa) channels and glibenclamide-sensitive adenosine triphosphate (ATP)-dependent K+ (K-ATP) channels. Thus, our results suggest that formononetin caused vascular relaxation via endothelium/NO-dependent mechanism and endothelium-independent mechanism which involves the activation of BKCa and K-ATP channels. (C) 2010 Elsevier Inc. All rights reserved.
All Author(s) ListWu JH, Li Q, Wu MY, Guo DJ, Chen HL, Chen SL, Seto SW, Au ALS, Poon CCW, Leung GPH, Lee SMY, Kwan YW, Chan SW
Journal nameJournal of Nutritional Biochemistry
Detailed descriptionTo ORKTS: doi: 10.1016/j.jnutbio.2009.03.010
Year2010
Month7
Day1
Volume Number21
Issue Number7
PublisherElsevier
Pages613 - 620
ISSN0955-2863
eISSN1873-4847
LanguagesEnglish-United Kingdom
KeywordsBKCa and K-ATP channels; Formononetin; Nitric oxide; Vasorelaxation
Web of Science Subject CategoriesBiochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Nutrition & Dietetics; NUTRITION & DIETETICS

Last updated on 2021-19-10 at 23:30