title: Effect of losartan, compared with atenolol, on endothelial function and oxidative stress in patients with type 2 diabetes and hypertension.
abstract: OBJECTIVE
  It has been shown that angiotensin-converting enzyme inhibition or angiotensin receptor blockade may improve endothelial dysfunction, an early manifestation of atherosclerosis, in patients with diabetes. Whether this protective effect is mediated through blood pressure-lowering effects or other specific mechanisms such as a reduction in oxidative stress is not clear. We investigated the influence of losartan, compared with atenolol, on endothelial function and oxidative stress in patients with type 2 diabetes and hypertension.
  
  
  METHODS
  Thirteen patients were included in this randomized, double-blind, crossover study; they received losartan 50 mg twice daily for 4 weeks followed by atenolol 50 mg twice daily or vice versa. Concomitant medication with renin-angiotensin blocking agents or beta-blockers was withdrawn, whereas other medication remained unchanged. At baseline and after each treatment period, flow-mediated dilation of the brachial artery and oxidative stress were measured in serum samples.
  
  
  RESULTS
  Flow-mediated dilation was increased significantly after 4 weeks' treatment with losartan (3.4 +/- 0.44%) compared with atenolol (2.58 +/- 0.42%; P = 0.01). 8-Isoprostanes, a marker of oxidative stress, were significantly reduced in the losartan group compared with baseline (0.039 +/- 0.007 versus 0.067 +/- 0.006 ng/ml; P = 0.01), but did not differ from baseline with atenolol. Glucose, hemoglobin A1c, highly sensitive C-reactive protein, lipids and systolic blood pressure remained unaltered, whereas diastolic blood pressure tended to be lower in the atenolol group.
  
  
  CONCLUSIONS
  This study demonstrates that losartan significantly improved endothelial function in type 2 diabetes patients with hypertension compared with atenolol. This must be independent of the blood pressure-lowering effect of losartan and is probably caused by an antioxidative effect of the angiotensin receptor blocker.
authors.affiliation: Cardiovascular Center, Cardiology, University Hospital Zurich, Switzerland.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Flammer
authors.forename: Frank
authors.initials: F
authors.lastname: Hermann
authors.forename: Peter
authors.initials: P
authors.lastname: Wiesli
authors.forename: Beat
authors.initials: B
authors.lastname: Schwegler
authors.forename: Rémy
authors.initials: R
authors.lastname: Chenevard
authors.forename: David
authors.initials: D
authors.lastname: Hürlimann
authors.forename: Isabella
authors.initials: I
authors.lastname: Sudano
authors.forename: Steffen
authors.initials: S
authors.lastname: Gay
authors.forename: Michel
authors.initials: M
authors.lastname: Neidhart
authors.forename: Walter
authors.initials: W
authors.lastname: Riesen
authors.forename: Frank
authors.initials: F
authors.lastname: Ruschitzka
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
authors.forename: Georg
authors.initials: G
authors.lastname: Noll
authors.forename: Roger
authors.initials: R
authors.lastname: Lehmann
mesh_terms: D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001262:Atenolol / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D007333:Insulin Resistance; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D012107:Research Design; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; C075750:8-epi-prostaglandin F2alpha; D001262:Atenolol; D015237:Dinoprost; D019808:Losartan