Acute and chronic angiotensin-1 receptor antagonism reverses endothelial dysfunction in atherosclerosis.
Circulation
; 101(20): 2349-54, 2000 May 23.
Article
em En
| MEDLINE
| ID: mdl-10821809
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. METHODS ANDRESULTS:
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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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Arteriosclerose
/
Endotélio Vascular
/
Losartan
/
Antagonistas de Receptores de Angiotensina
Tipo de estudo:
Clinical_trials
/
Etiology_studies
Limite:
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Circulation
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Estados Unidos