title: Fixed-dose combination of losartan and hydrochlorothiazide significantly improves endothelial function in uncontrolled hypertension by low-dose amlodipine: a randomized study.
abstract: OBJECTIVE
  Flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) in the brachial artery are well-known indices for evaluating endothelial function (ECF). The blood pressure-lowering effects of the combination of losartan (ARB) and low-dose hydrochlorothiazide (H: ARB-H; ARB, 50 mg and H, 12.5 mg) are useful. The aim of the present study was to examine whether the combination of losartan and low-dose hydrochlorothiazide could improve ECF.
  
  
  METHODS
  To investigate the effect of ARB-H on ECF in patients with uncontrolled hypertension despite the use of amlodipine (2.5 mg daily), we performed a randomized controlled open-labeled study by using the envelope method and assigned 42 patients to either a control (CTRL) group or an ARB-H combination group, both of which received amlodipine 2.5 mg daily during the treatment period. In addition, both the CTRL (n=21, 69±7 years old) and ARB-H groups (n=21, 69±7 years old) received additional behavioral modification. Before and after 8 weeks of therapy, FMD and NMD were measured in both groups using novel FMD equipment (UNEXEF18G).
  
  
  RESULTS
  Although baseline FMD was not different between the two groups, post-therapy FMD increased in the ARB-H group (2.97±1.56 to 3.95±1.86%, p<0.05) but did not change significantly in the CTRL group (2.95±1.43 to 3.11±1.27%, NS). No significant change was seen in NMD when comparing baseline and post-therapy values in either group. No treatment complications were observed.
  
  
  CONCLUSIONS
  A fixed-dose combination of losartan and hydrochlorothiazide enhances ECF, suggesting that this combination might have both anti-hypertensive and anti-atherosclerotic effects in patients with hypertension.
authors.affiliation: Department of Intensive Care Medicine, National Defense Medical College; Saitama-Japan. bonpeit@ndmc.ac.jp.
authors.forename: Bonpei
authors.initials: B
authors.lastname: Takase
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Nagata
mesh_terms: D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001916:Brachial Artery / Q000503:physiopathology*; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy*; D019808:Losartan / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D011673:Pulsatile Flow; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D017311:Amlodipine; D019808:Losartan