| Acute and chronic angiotensin-1 receptor antagonism reverses endothelial dysfunction in atherosclerosis. | |
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MedLine Citation:
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PMID: 10821809 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. METHODS AND 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. |
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Authors:
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A Prasad; T Tupas-Habib; W H Schenke; R Mincemoyer; J A Panza; M A Waclawin; S Ellahham; A A Quyyumi |
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Publication Detail:
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Type: Clinical Trial; Journal Article |
Journal Detail:
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Title: Circulation Volume: 101 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2000 May |
Date Detail:
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Created Date: 2000-06-21 Completed Date: 2000-06-21 Revised Date: 2004-11-17 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 2349-54 Citation Subset: AIM; IM |
Affiliation:
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Cardiology Branch, Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcholine
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pharmacology Angiotensin II / pharmacology Arteriosclerosis / complications, drug therapy*, physiopathology Brachial Artery / physiopathology Endothelium, Vascular / drug effects*, physiopathology Female Femoral Artery / physiopathology Humans Hyperemia / etiology, physiopathology Losartan / therapeutic use* Male Middle Aged Nitroprusside / pharmacology Receptor, Angiotensin, Type 1 Receptor, Angiotensin, Type 2 Receptors, Angiotensin / antagonists & inhibitors* Regional Blood Flow / drug effects Single-Blind Method Time Factors Vascular Resistance / drug effects Vasodilation / drug effects Vasodilator Agents / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Receptor, Angiotensin, Type 1; 0/Receptor, Angiotensin, Type 2; 0/Receptors, Angiotensin; 0/Vasodilator Agents; 11128-99-7/Angiotensin II; 114798-26-4/Losartan; 15078-28-1/Nitroprusside; 51-84-3/Acetylcholine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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