Formononetin, an isoflavone, relaxes rat isolated aorta through endothelium-dependent and endothelium-independent pathways

Jian Hong Wu, Qing Li, Min Yi Wu, De Jian Guo, Huan Le Chen, Shi Lin Chen, Sai Wang Seto, Alice L.S. Au, Christina C.W. Poon, George P.H. Leung, Simon M.Y. Lee, Yiu Wa Kwan, Shun Wan Chan

Research output: Journal article publicationJournal articleAcademic researchpeer-review

73 Citations (Scopus)

Abstract

We 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 μM) and methylene blue (10 μM) 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-eNOSSer1177 protein expression. In endothelium-denuded preparations, formononetin-induced vasorelaxation was significantly reduced by glibenclamide (3 μM) and iberiotoxin (100 nM), and a combination of glibenclamide (3 μM) plus iberiotoxin (100 nM) abolished the relaxation. In contrast, formononetin-elicited endothelium-independent relaxation was not altered by ICI 182,780 (10 μM, an estrogen receptor (ERα/ERβ) antagonist) or mifepristone (10 μM, 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+ (KATP) 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 KATP channels.

Original languageEnglish
Pages (from-to)613-620
Number of pages8
JournalJournal of Nutritional Biochemistry
Volume21
Issue number7
DOIs
Publication statusPublished - Jul 2010

Keywords

  • Formononetin
  • Nitric oxide
  • Vasorelaxation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

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