Mechanisms Underlying Biochanin A‐induced Relaxation of the Aorta Differ Between Normotensive and Hypertensive Rats

Abstract

1. The aim of the present study was to investigate the mechanism underlying biochanin A-induced relaxation of the aorta in spontaneously hypertensive rats (SHR). 2. The tension in isolated ring preparations of thoracic aortas from normotensive (Wistar-Kyoto (WKY) rats) and SHR at 5 and 10 weeks of age was measured isometrically. 3. Biochanin A (10(-7) to 10(-4) mol/L) induced a concentration-dependent relaxation in aortic rings from both strains at the age of 5 and 10 weeks and the relaxation was greater in rings from 10-week-old SHR compared with age-matched WKY rats. The vasorelaxation induced by biochanin A was significantly reduced by denudation of the endothelium in aortic rings from SHR, but not WKY rats. Treatment with either indomethacin, a cyclo-oxygenase inhibitor, or N(omega)-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, had little effect on the relaxation induced by biochanin A in aortic rings from either strain. Glibenclamide, a selective inhibitor of ATP-sensitive potassium channels, significantly attenuated the relaxation induced by biochanin A in aortic rings from both strains, although the extent of reduction was greater in WKY rats than SHR. Conversely, treatment with 4-aminopyridine, a selective inhibitor of voltage-dependent potassium channels, or tetraethylammonium, an inhibitor of calcium-activated potassium channels, significantly reduced the vasorelaxation induced by biochanin A in rings from SHR but not WKY rats. 4. The greater vasorelaxation produced by biochanin A in aortic rings from 10-week-old SHR is endothelium dependent. Different mechanisms underlie the relaxant effects of biochanin A in aorta from SHR and WKY rats. The mechanisms of biochanin A-induced vasorelaxation in thoracic aortas from both normotensive and hypertensive rats involve ATP-sensitive potassium channels and, in addition, in rings from the hypertensive strain at 10 weeks of age, an endothelium-derived activation of smooth muscle cell potassium channels contributes to the vasorelaxation observed.

Biochanin A, the Most Potent of 16 Isoflavones, Induces Relaxation of the Coronary Artery Through the Calcium Channel and cGMP-dependent Pathway

“…Considering that the effects of both are inhibited by biochanin A, we presumed that this isoflavonoid rather acts on downstream contraction pathways than on the receptor level. Biochanin A (1-10 µM) also managed to inhibit the contractions induced by phenylephrine, another agonist on Gq proteincoupled receptors, in rat aortas [25]. Similarly, in this study, biochanin A caused the vasodilation of norepinephrine precontracted vessels in the same experimental model (▶ Fig.…”

“…In the case of biochanin A, more data showing its vasorelaxing properties are available. These include rabbit coronary and basilar arteries [11,15], as well as rat aortas [8,25]. Biochanin A induces dose-dependent and endothelium-independent relaxation.…”

“…Although these aforementioned studies confirmed the effects of biochanin, the precise mechanism of action was unknown. Before this study was initiated, there was rather only negative evidence reporting that biochanin A did not affect the production of nitric oxide or prostaglandins [8,25]. The only known mechanism of action was a partial effect of biochanin A on the activation of ATP-sensitive and large-conductance Ca 2+ -activated K + channels [8,25].…”

“…Before this study was initiated, there was rather only negative evidence reporting that biochanin A did not affect the production of nitric oxide or prostaglandins [8,25]. The only known mechanism of action was a partial effect of biochanin A on the activation of ATP-sensitive and large-conductance Ca 2+ -activated K + channels [8,25]. Since these effects cannot fully explain the ability of this compound to evoke complete or almost complete relaxation of the tested vessels, the mechanism of action was further sought.…”

Development and characterization of enteric-coated microparticles of biochanin A for their beneficial pharmacological potential in estrogen deficient-hypertension

“…Furthermore, Wang et al subsequently confirmed that biochanin A induces endothelium-independent relaxation in rat aortic rings by blockage of Ca 2+ entry through the cell membrane and activation of K + channels. In spontaneously hypertensive rats, biochanin A-induced vasorelaxation was increased than in normotensive rats, which was mediated by the release of endothelium-derived substances that may open voltage-dependent and Ca 2+ activated K channels in the vascular smooth muscle (Wang et al, 2006). BCA is an isoflavanoid and it has also been revealed that flavonoids could be incorporated into the plasma membrane and cytosol of endothelial cells and are beneficial for scavenging ROS (Youdim et al, 2000).…”