Effects of angiotensin II type 1-receptor blockade on retinal endothelial function.
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.
Ott
Christian
C
Department of Nephrology and Hypertension, University of Erlangen-Nürnberg, Germany.
Schlaich
Markus P
MP
Harazny
Joanna
J
Schmidt
Bernhard Mw
BM
Michelson
Georg
G
Schmieder
Roland E
RE
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*
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000077405:Irbesartan