title: Effects of angiotensin II type 1-receptor blockade on retinal endothelial function.
abstract: OBJECTIVE
  Hypercholesterolemia is an important risk factor for atherosclerotic vascular disease including stroke. Low-density lipoprotein-cholesterol may induce upregulation of angiotensin II type 1 (AT1)-receptors and their activation plays a pathogenetic role in atherosclerosis, possibly via enhanced breakdown of nitric oxide. We tested whether AT1-receptor blockade improved endothelial function of the retinal vasculature in normocholesterolemic and hypercholesterolemic subjects.
  
  
  METHODS
  Thirty-one hypercholesterolemic and 17 normocholesterolemic subjects were randomly assigned to treatment with irbesartan and placebo in a double-blind crossover study. Retinal capillary flow was measured using scanning laser Doppler flowmetry. Diffuse luminance flicker was applied to provoke vasodilation that is in part nitric oxide dependent.
  
  
  RESULTS
  Flicker-induced increases in retinal capillary flow were similar between hypercholesterolemic and normocholesterolemic subjects. In contrast to placebo, treatment with irbesartan led to a significant reduction of blood pressure, in our patients with normal blood pressure values. Therefore we divided our study cohort according to the median blood pressure reduction in response to irbesartan. Flicker-induced increases in retinal capillary flow were substantially higher in subjects with a systolic blood pressure reduction above median (> 6 mmHg) than in those with a reduction below median (<or=6 mmHg) (16.2 +/- 16% versus 6.88 +/- 11%; P = 0.042).
  
  
  CONCLUSIONS
  AT1-receptor blockade with irbesartan improves endothelial function of the retinal vasculature, taken as a model of cerebral circulation.
authors.affiliation: Department of Nephrology and Hypertension, University of Erlangen-Nürnberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Ott
authors.forename: Markus P
authors.initials: MP
authors.lastname: Schlaich
authors.forename: Joanna
authors.initials: J
authors.lastname: Harazny
authors.forename: Bernhard Mw
authors.initials: BM
authors.lastname: Schmidt
authors.forename: Georg
authors.initials: G
authors.lastname: Michelson
authors.forename: Roland E
authors.initials: RE
authors.lastname: Schmieder
mesh_terms: D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000503:physiopathology*; D000077405:Irbesartan; D017078:Laser-Doppler Flowmetry; D008297:Male; D008875:Middle Aged; D012039:Regional Blood Flow / Q000187:drug effects; D012171:Retinal Vessels / Q000187:drug effects* / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000077405:Irbesartan