title: A Combination of Intravenous Genistein Plus Mg2+ Enhances Antihypertensive Effects in SHR by Endothelial Protection and BKCa Channel Inhibition.
abstract: BACKGROUND
  The effects of combining genistein (GST) plus magnesium (Mg) upon the development of hypertension were examined in 28 twelve-week-old male spontaneous hypertension rats (SHRs). Four experimental groups were tested: SHR (0.9% NaCl and DMSO), SHR + GST (0.9% NaCl and GST 5mg/kg/day), SHR + Mg (Mg(2+) 0.75 mmol/kg/day and DMSO), and SHR + GST + Mg (Mg(2+) 0.75 mmol/kg/day and GST 5mg/kg/day). A group of normotensive genetic control, Wistar-Kyoto (WKY) rats were also included for comparison. Drugs were administrated intravenously daily for 30 days.
  
  
  METHODS
  Systolic blood pressure (SBP) and heart rate were measured by tail-cuff plethysmography every five days. Vascular tone of mesenteric arteries was examined by an isometric force transducer. Big-conductance calcium-activated potassium channel (BKCa) currents were detected by whole-cell patch-clamp techniques.
  
  
  RESULTS
  SBP in SHRs was significantly elevated vs. that in WKY rats. GST or Mg lowered SBP of SHRs. Their combination enhanced antihypertensive effects, as indicated by significantly lowered SBP and shorter onset times. GST or Mg individually improved endothelial dysfunction of SHRs. However, again their combination enhanced endothelial protection, nearly restoring maximal relaxation responses to those seen in WKY. BKCa currents in SHRs were increased compared with WKY rats. GST, Mg, and their combination restored BKCa currents to those of WKY rats.
  
  
  CONCLUSIONS
  The combination of GST and Mg produces antihypertensive effects and improvement of endothelial dysfunction, which are substantially greater than that when either is used individually. These results suggest a novel and feasible protocol for the prevention and treatment of hypertension and related cardio- and cerebro-vascular diseases.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China;
authors.forename: Lina
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China;
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China;
authors.forename: Ting
authors.initials: T
authors.lastname: Ju
authors.affiliation: Department of Physiology, Harbin Medical University, Harbin 150086, China.
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China;
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China;
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China; zfx0001@126.com.
authors.forename: Liming
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China;
authors.forename: Guichun
authors.initials: G
authors.lastname: Yu
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D019833:Genistein / Q000008:administration & dosage*; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007275:Injections, Intravenous; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015636:Magnesium Chloride / Q000008:administration & dosage*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D026902:Potassium Channel Blockers / Q000008:administration & dosage*; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors
chemical_list: C494842:Kcnma1 protein, rat; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D026902:Potassium Channel Blockers; D015636:Magnesium Chloride; D019833:Genistein
keywords: big-conductance calcium-activated potassium channels; blood pressure; endothelial function; genistein; hypertension; magnesium; systolic blood pressure.