title: Effect of antihypertensive treatment with candesartan or amlodipine on glutathione and its redox status, homocysteine and vitamin concentrations in patients with essential hypertension.
abstract: OBJECTIVE
  To compare the effect of candesartan or amlodipine on concentrations of cellular markers of oxidative stress, plasma homocysteine and vitamins in hypertensive patients.
  
  
  METHODS
  Forty-nine middle-aged patients with untreated stage I-II essential hypertension were recruited in a randomized double-blind double-dummy study to receive a daily dose either of 8 mg candesartan (n = 25) or 5 mg amlodipine (n = 24) for 16 weeks. Blood pressure, reduced glutathione (GSH) and oxidized glutathione (GSSG), glutathione redox ratio (GSSG : GSH) in red blood cells, plasma homocysteine, vitamin B12 and folic acid status were measured at baseline, at week 2 and at week 16. The same parameters were measured in 32 healthy age- and sex-matched controls. An increase in homocysteine of at least 2 micromol/l was considered significant.
  
  
  RESULTS
  Hypertensive patients had significantly greater oxidative stress and homocysteine concentrations than controls. In addition to a significant decrease in blood pressure, in both treatment groups GSSG decreased (P < 0.03), GSSG : GSH had a tendency to decrease (P = 0.054), but homocysteine did not change. An increase in homocysteine concentration of at least 2 micromol/l was found in 12 patients (five in the candesartan group, seven in the amlodipine group), with a significant decrease in folic acid concentration and no changes in cellular oxidative stress. In patients with no increase in homocysteine concentration, both GSSG (P < 0.02) and GSSG : GSH (P = 0.051) decreased. GSH and vitamin B12 did not change in any of the groups studied.
  
  
  CONCLUSIONS
  Untreated hypertension is associated with disturbed glutathione redox status and increased plasma homocysteine concentrations. Both candesartan and amlodipine had favourable effects on cellular oxidative stress, but the oxidative stress status did not decrease in patients with adverse changes in homocysteine.
authors.affiliation: Department of Cardiology, University of Tartu, Tartu, Estonia. Piibe.Muda@kliinikum.ee
authors.forename: Piibe
authors.initials: P
authors.lastname: Muda
authors.forename: Priit
authors.initials: P
authors.lastname: Kampus
authors.forename: Mihkel
authors.initials: M
authors.lastname: Zilmer
authors.forename: Tiina
authors.initials: T
authors.lastname: Ristimäe
authors.forename: Krista
authors.initials: K
authors.lastname: Fischer
authors.forename: Kersti
authors.initials: K
authors.lastname: Zilmer
authors.forename: Ceslava
authors.initials: C
authors.lastname: Kairane
authors.forename: Rein
authors.initials: R
authors.lastname: Teesalu
mesh_terms: D017311:Amlodipine / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005492:Folic Acid / Q000097:blood*; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D013777:Tetrazoles / Q000008:administration & dosage*; D014805:Vitamin B 12 / Q000097:blood*
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D006710:Homocysteine; D017311:Amlodipine; D005492:Folic Acid; D005978:Glutathione; D014805:Vitamin B 12; C081643:candesartan; D019803:Glutathione Disulfide