Inhibition of the AT1 receptor with losartan reversed endothelial dysfunction in patients with atherosclerosis, improving flow-mediated brachial artery dilation from 1.4% to 3.2% (P=0.03).
Does losartan improve endothelial dysfunction in patients with atherosclerosis?
Angiotensin-1 receptor antagonism with losartan reverses endothelial dysfunction in patients with atherosclerosis by improving nitric oxide availability.
Tasa de eventos absoluta: 3.2% vs 1.4%
valor p: p=0.03
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.
Prasad et al. (Tue,) conducted a other in Atherosclerosis (n=59). Losartan vs. Baseline (before administration) and control subjects was evaluated on Flow-mediated brachial artery dilation (p=0.03). Inhibition of the AT1 receptor with losartan reversed endothelial dysfunction in patients with atherosclerosis, improving flow-mediated brachial artery dilation from 1.4% to 3.2% (P=0.03).
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