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 (AT1) 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 μg/min, P<0.001) but not control subjects. Vasodilation during reactive hyperemia was also greater after AT1 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 μmol/L (P=0.008). Conclusions - The results of the present study indicate that inhibition of the AT1 receptor in patients with atherosclerosis reverses endothelial dysfunction by improving NO availability and therefore may have long-term therapeutic benefits.
Original language | English (US) |
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Pages (from-to) | 2349-2354 |
Number of pages | 6 |
Journal | Circulation |
Volume | 101 |
Issue number | 20 |
DOIs | |
State | Published - May 23 2000 |
Keywords
- Angiotensin
- Atherosclerosis
- Endothelium
- Losartan
- Nitric oxide
- Receptors
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)