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

• Published in: The Journal of nutritional biochemistry 2010-07, Vol.21 (7), p.613-620
• Main Authors: Wu, Jian-Hong, Li, Qing, Wu, Min-Yi, Guo, De-Jian, Chen, Huan-Le, Chen, Shi-Lin, Seto, Sai-Wang, Au, Alice L.S., Poon, Christina C.W., Leung, George P.H., Lee, Simon M.Y., Kwan, Yiu-Wa, Chan, Shun-Wan
• Format: Article
• Language: English
• Subjects: Animals; Aorta, Thoracic; Biological and medical sciences; BK Ca and K ATP channels; Cardiovascular Diseases - drug therapy; Cardiovascular Diseases - prevention & control; Cells, Cultured; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; Enzyme Inhibitors - pharmacology; Feeding. Feeding behavior; Formononetin; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Isoflavones - pharmacology; Male; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Nitric oxide; Nitric Oxide Synthase Type II - antagonists & inhibitors; Nitric Oxide Synthase Type II - metabolism; Nitric Oxide Synthase Type III - antagonists & inhibitors; Nitric Oxide Synthase Type III - genetics; Nitric Oxide Synthase Type III - metabolism; Osmolar Concentration; Phytoestrogens - pharmacology; Phytotherapy; Rats; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Up-Regulation - drug effects; Vasodilation - drug effects; Vasodilator Agents - pharmacology; Vasorelaxation; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2009.03.010

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-eNOS Ser1177 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 Ca 2+-activated K + (BK Ca) 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 BK Ca and K ATP channels.