title: Effects of low dietary magnesium intake on development of hypertension in stroke-prone spontaneously hypertensive rats: role of reactive oxygen species.
abstract: OBJECTIVE
  To investigate whether low dietary Mg2+ intake influences the development of hypertension in stroke-prone spontaneously hypertensive rats (spSHRs) and whether these effects are associated with vascular functional and structural changes, and to assess the role of reactive oxygen species and the activation of vascular mitogen-activated protein (MAP) kinases in these processes.
  
  
  METHODS
  Six-week-old male spSHRs (n = 18) were divided into three groups: control (normal chow, 0.21% Mg2+ ), low Mg2+ group (Mg2+ -free diet), and high Mg2+ group (Mg2+ -rich diet, 0.75%). Systolic blood pressure (SBP) was assessed weekly for 16 weeks. In a second series of experiments, 6-week-old spSHRs (n = 18) were divided into three groups and studied weekly for 7 weeks: control group, low Mg2+ group, and low Mg2+ group receiving the superoxide dismutase mimetic, tempol (1 mmol/l).
  
  
  RESULTS
  The low Mg2+ diet caused an initial decrease in SBP followed, 5 weeks later, by an exacerbated development of hypertension. This was associated with a transient reduction in the plasma concentrations of substances associated with the thiobarbituric acid reaction (markers of oxidative stress), which increased rapidly 2 weeks later. In the low Mg2+ group, acetylcholine-induced vasodilatation was decreased compared with that in controls ( P<0.05). The media : lumen ratio was greater in rats receiving a low Mg2+ diet than in those fed a high Mg2+ diet ( P<0.05). Mg2+ depletion was associated with increased vascular superoxide anion compared with that in Mg2+ -supplemented rats (1.2 0.24 compared with 0.65 0.1 nmol/min per mg). Phosphorylation of MAP kinases was increased two- to threefold in Mg2+ -deficient rats. Tempol prevented the progression of hypertension and normalized the vascular changes in rats fed a low Mg2+ diet.
  
  
  CONCLUSIONS
  Chronic Mg2+ deficiency leads to development of severe hypertension, endothelial dysfunction and vascular remodelling. These processes are associated with oxidative stress and upregulation of redox-dependent MAP kinases. Tempol normalized vascular changes and attenuated the development of hypertension. Our findings suggest that reactive oxygen species play an important part in vascular processes that are associated with progression of hypertension in Mg2+ -deficient spSHRs.
authors.affiliation: Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Canada. touyzr@ircm.qc.ca
authors.forename: Rhian M
authors.initials: RM
authors.lastname: Touyz
authors.forename: Qian
authors.initials: Q
authors.lastname: Pu
authors.forename: Gang
authors.initials: G
authors.lastname: He
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Guoying
authors.initials: G
authors.lastname: Yao
authors.forename: Mario Fritsch
authors.initials: MF
authors.lastname: Neves
authors.forename: Emilie
authors.initials: E
authors.lastname: Viel
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000097:blood; D002908:Chronic Disease; D006973:Hypertension / Q000097:blood* / Q000209:etiology*; D048031:JNK Mitogen-Activated Protein Kinases; D008274:Magnesium / Q000097:blood / Q000494:pharmacology*; D008275:Magnesium Deficiency / Q000097:blood / Q000150:complications*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018384:Oxidative Stress; D010766:Phosphorylation / Q000187:drug effects; D011188:Potassium / Q000097:blood; D051381:Rats; D011918:Rats, Inbred SHR; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012964:Sodium / Q000097:blood; D020521:Stroke / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D012964:Sodium; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D008274:Magnesium; D011188:Potassium; D002118:Calcium