title: Acute and chronic angiotensin-1 receptor antagonism reverses endothelial dysfunction in atherosclerosis.
abstract: BACKGROUND
  The renin-angiotensin system may contribute to atherogenesis through the promotion of endothelial dysfunction. The present study was performed to determine whether angiotensin-1 (AT(1)) receptor inhibition improves endothelial dysfunction.
  
  
  RESULTS
  In the femoral circulation of 19 patients with atherosclerosis and of 9 control subjects, we studied microvascular responses to reactive hyperemia, angiotensin II, acetylcholine, and sodium nitroprusside before and after the administration of intra-arterial losartan (10 mg). Femoral artery flow velocity was measured with a Doppler flow wire, and the femoral vascular resistance index (FVRI) was calculated as mean arterial pressure divided by flow velocity. Losartan induced a minor (5.9+/-2%, P=0. 02) reduction in FVRI and inhibited angiotensin II-mediated vasoconstriction in both patient groups (P<0.01). After the administration of losartan, acetylcholine-mediated vasodilation was augmented in patients (44+/-5% to 58+/-4% reduction in FVRI with infusion at a rate of 150 microgram/min, P<0.001) but not control subjects. Vasodilation during reactive hyperemia was also greater after AT(1) receptor inhibition (P=0.03) in patients, but the response to sodium nitroprusside remained unchanged. In a separate group of 31 patients with atherosclerosis, we investigated the effect of 8 weeks of oral losartan therapy on brachial artery flow-mediated vasodilation with the use of high-resolution ultrasound. Oral losartan therapy improved flow-mediated brachial artery dilation (1.4+/-0.9% to 3.2+/-0.8%, P=0.03) but had no effect on the nitroglycerin response. Serum nitrogen oxide levels increased from 21.6+/-1.7 to 26.7+/-2.4 micromol/L (P=0.008).
  
  
  CONCLUSIONS
  The results of the present study indicate that inhibition of the AT(1) receptor in patients with atherosclerosis reverses endothelial dysfunction by improving NO availability and therefore may have long-term therapeutic benefits.
authors.affiliation: Cardiology Branch, Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: A
authors.initials: A
authors.lastname: Prasad
authors.forename: T
authors.initials: T
authors.lastname: Tupas-Habib
authors.forename: W H
authors.initials: WH
authors.lastname: Schenke
authors.forename: R
authors.initials: R
authors.lastname: Mincemoyer
authors.forename: J A
authors.initials: JA
authors.lastname: Panza
authors.forename: M A
authors.initials: MA
authors.lastname: Waclawin
authors.forename: S
authors.initials: S
authors.lastname: Ellahham
authors.forename: A A
authors.initials: AA
authors.lastname: Quyyumi
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D001161:Arteriosclerosis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D001916:Brachial Artery / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D005263:Femoral Artery / Q000503:physiopathology; D006801:Humans; D006940:Hyperemia / Q000209:etiology / Q000503:physiopathology; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012039:Regional Blood Flow / Q000187:drug effects; D016037:Single-Blind Method; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D014665:Vasodilator Agents; D000804:Angiotensin II; D009599:Nitroprusside; D019808:Losartan; D000109:Acetylcholine