title: A combination of genistein and magnesium enhances the vasodilatory effect via an eNOS pathway and BK(Ca) current amplification.
abstract: The phytoestrogen genistein (GST) and magnesium have been independently shown to regulate vascular tone; however, their individual vasodilatory effects are limited. The aim of this study was to examine the combined effects of GST plus magnesium on vascular tone in mesenteric arteries. The effects of pretreatment with GST (0-200 μmol/L), MgCl2 (0-4.8 mmol/L) and GST plus MgCl2 on 10 μmol/L phenylephrine (PE) precontracted mesenteric arteries in rats were assessed by measuring isometric force. BK(Ca) currents were detected by the patch clamp method. GST caused concentration- and partial endothelium-dependent relaxation. Magnesium resulted in dual adjustment of vascular tone. Magnesium-free solution eliminated the vasodilatation of GST in both endothelium-intact and denuded rings. GST (50 μmol/L) plus magnesium (4.8 mmol/L) caused stronger relaxation in both endothelium-intact and denuded rings. Pretreatment with the nitric oxide synthase (NOS) inhibitor L-N-nitroarginine methyl ester (L-NAME, 100 μmol/L) significantly inhibited the effects of GST, high magnesium, and the combination of GST and magnesium. BK(Ca) currents were amplified to a greater extent when GST (50 μmol/L) was combined with 4.8 versus 1.2 mmol/L Mg(2+). Our data suggest that GST plus magnesium provides enhanced vasodilatory effects in rat mesenteric arteries compared with that observed when either is used separately, which was related to an eNOS pathway and BK(Ca) current amplification.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, 23 Post Street, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Lina
authors.initials: L
authors.lastname: Sun
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Hou
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhao
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhou
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Wang
authors.forename: Liming
authors.initials: L
authors.lastname: Zhang
authors.forename: Guichun
authors.initials: G
authors.lastname: Yu
mesh_terms: D000818:Animals; D019587:Dietary Supplements; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000378:metabolism*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000819:agonists* / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D017538:Mesenteric Artery, Superior; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D048789:Phytoestrogens / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; C494842:Kcnma1 protein, rat; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D048789:Phytoestrogens; D019833:Genistein; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D008274:Magnesium
keywords: cellule de muscle lisse; electrophysiology; endothelium; endothélium; phytoestrogen; phytoestrogène; régulation vasculaire; smooth muscle cell; vascular regulation; électrophysiologie