Kidney Res Clin Pract.  2014 Dec;33(4):181-186. 10.1016/j.krcp.2014.08.003.

Mechanisms of phytoestrogen biochanin A-induced vasorelaxation in renovascular hypertensive rats

• Choi S
• Jung WS
• Cho NS
• Ryu KH
• Jun JY
• Shin BC
• Chung JH
• Yeum CH

• KMID: 2224258
• DOI: http://doi.org/10.1016/j.krcp.2014.08.003

Abstract

BACKGROUND
The plant-derived estrogen biochanin A is known to cause vasodilation, but its mechanism of action in hypertension remains unclear. This study was undertaken to investigate the effects and mechanisms of biochanin A on the thoracic aorta in two-kidney, one clip (2K1C) renovascular hypertensive rats.
METHODS
Hypertension was induced by clipping the left renal artery, and control age-matched rats were sham treated. Thoracic aortae were mounted in tissue baths to measure isometric tension.
RESULTS
Biochanin A caused concentration-dependent relaxation in aortic rings from 2K1C hypertensive and sham-treated rats, which was greater in 2K1C rats than in sham rats. Biochanin A-induced relaxation was significantly attenuated by removing the endothelium in aortic rings from 2K1C rats, but not in sham rats. Nomega-Nitro-L-arginine methylester, a nitric oxide synthase inhibitor, or indomethacin, a cyclooxygenase inhibitor, did not affect the biochanin A-induced relaxation in aortic rings from 2K1C and sham rats. By contrast, treatment with glibenclamide, a selective inhibitor of adenosine triphosphate-sensitive K+ channels, ortetraethy-lammonium, an inhibitor of Ca2+-activated K+ channels, significantly reduced biochanin A-induced relaxation in aortic rings from both groups. However, 4-aminopyridine, a selective inhibitor of voltage-dependent K+ channels, inhibited the relaxation induced by biochanin A in 2K1C rats, whereas no significant differences were observed in sham rats.
CONCLUSION
These results suggest that the enhanced relaxation caused by biochanin A in aortic rings from hypertensive rats is endothelium dependent. Vascular smooth muscle K+ channels may be involved in biochanin A-induced relaxation in aortae from hypertensive and normotensive rats. In addition, an endothelium-derived activation of voltage-dependent K+ channels contributes, at least in part, to the relaxant effect of biochanin A in renovascular hypertension.

Keyword

Biochanin A; Endothelium; K+ channels; Renovascular hypertension

MeSH Terms

4-Aminopyridine
Adenosine
Animals
Aorta
Aorta, Thoracic
Baths
Endothelium
Estrogens
Glyburide
Hypertension
Hypertension, Renovascular
Indomethacin
Muscle, Smooth, Vascular
Nitric Oxide Synthase
Phytoestrogens*
Potassium Channels, Calcium-Activated
Prostaglandin-Endoperoxide Synthases
Rats*
Relaxation
Renal Artery
Vasodilation*
4-Aminopyridine
Adenosine
Estrogens
Glyburide
Indomethacin
Nitric Oxide Synthase
Phytoestrogens
Potassium Channels, Calcium-Activated
Prostaglandin-Endoperoxide Synthases