title: Equol increases cerebral blood flow in rats via activation of large-conductance Ca(2+)-activated K(+) channels in vascular smooth muscle cells.
abstract: The present study was designed to investigate the effect of equol on cerebral blood flow and the underlying molecular mechanisms. The regional cerebral blood flow in parietal lobe of rats was measured by using a laser Doppler flowmetry. Isolated cerebral basilar artery and mesenteric artery rings from rats were used for vascular reactivity measurement with a multi wire myography system. Outward K(+) current in smooth muscle cells of cerebral basilar artery, large-conductance Ca(2+)-activated K(+) (BK) channel current in BK-HEK 293 cells stably expressing both human α (hSlo)- and β1-subunits, and hSlo channel current in hSlo-HEK 293 cells expressing only the α-subunit of BK channels were recorded with whole cell patch-clamp technique. The results showed that equol significantly increased regional cerebral blood flow in rats, and produced a concentration-dependent but endothelium-independent relaxation in rat cerebral basilar arteries. Both paxilline and iberiotoxin, two selective BK channel blockers, significantly inhibited equol-induced vasodilation in cerebral arteries. Outward K(+) currents in smooth muscle cells of cerebral basilar artery were increased by equol and fully reversed by washout or blockade of BK channels with iberiotoxin. Equol remarkably enhanced human BK current in BK-HEK 293 cells, but not hSlo current in hSlo-HEK 293 cells, and the increase was completely abolished by co-application of paxilline. Our findings provide the first information that equol selectively stimulates BK channel current by acting on its β1 subunit, which may in turn contribute to the equol-mediated vasodilation and cerebral blood flow increase.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi⿿an Jiaotong University Health Science Center, 76 West Yanta Road, Xi⿿an 710061, Shaanxi, China; Cardiovascular Research Center, School of Basic Medical Sciences, Xi⿿an Jiaotong University Health Science Center, 76 West Yanta Road, Xi⿿an 710061, Shaanxi, China; Department of Physiology, Xi⿿an Medical University, 1 Xinwang Road, Xi⿿an 710021, Shaanxi, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi⿿an Jiaotong University Health Science Center, 76 West Yanta Road, Xi⿿an 710061, Shaanxi, China; Cardiovascular Research Center, School of Basic Medical Sciences, Xi⿿an Jiaotong University Health Science Center, 76 West Yanta Road, Xi⿿an 710061, Shaanxi, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi⿿an Jiaotong University Health Science Center, 76 West Yanta Road, Xi⿿an 710061, Shaanxi, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi⿿an Jiaotong University Health Science Center, 76 West Yanta Road, Xi⿿an 710061, Shaanxi, China; Cardiovascular Research Center, School of Basic Medical Sciences, Xi⿿an Jiaotong University Health Science Center, 76 West Yanta Road, Xi⿿an 710061, Shaanxi, China.
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Zhao
authors.affiliation: Xiamen Heart Center, Xiamen University, 201 South Hubin Road, Xiamen 361004, Fujian, China.
authors.forename: Gui-Rong
authors.initials: GR
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi⿿an Jiaotong University Health Science Center, 76 West Yanta Road, Xi⿿an 710061, Shaanxi, China; Cardiovascular Research Center, School of Basic Medical Sciences, Xi⿿an Jiaotong University Health Science Center, 76 West Yanta Road, Xi⿿an 710061, Shaanxi, China. Electronic address: dengxl@mail.xjtu.edu.cn.
authors.forename: Xiu-Ling
authors.initials: XL
authors.lastname: Deng
mesh_terms: D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D060754:Equol / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D066298:In Vitro Techniques; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000235:genetics / Q000502:physiology; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000235:genetics / Q000502:physiology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D021122:Protein Subunits / Q000235:genetics / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D021122:Protein Subunits; D014665:Vasodilator Agents; D060754:Equol
keywords: Cerebral basilar artery; Cerebral blood flow; Equol; Large-conductance Ca(2+)-activated K(+) channel; β1 subunit