Prasad A, Tupas-Habib T, Schenke W H, Mincemoyer R, Panza J A, Waclawin M A, Ellahham S, Quyyumi A A
Cardiology Branch, Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Circulation. 2000 May 23;101(20):2349-54. doi: 10.1161/01.cir.101.20.2349.
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.
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).
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.
肾素-血管紧张素系统可能通过促进内皮功能障碍而导致动脉粥样硬化的发生。本研究旨在确定血管紧张素1（AT(1)）受体抑制是否能改善内皮功能障碍。
在19例动脉粥样硬化患者和9例对照受试者的股循环中，我们研究了动脉内给予氯沙坦（10mg）前后，微血管对反应性充血、血管紧张素II、乙酰胆碱和硝普钠的反应。用多普勒血流导线测量股动脉血流速度，并计算股血管阻力指数（FVRI），即平均动脉压除以血流速度。氯沙坦使FVRI轻度降低（5.9±2%，P = 0.02），并抑制了两组患者中血管紧张素II介导的血管收缩（P<0.01）。给予氯沙坦后，患者乙酰胆碱介导性血管舒张增强（以150微克/分钟的速率输注时，FVRI降低从44±5%至58±4%，P<0.001），而对照受试者无此变化。在患者中，AT(受体抑制后反应性充血期间的血管舒张也增强（P = 0.03），但对硝普钠的反应保持不变。在另一组31例动脉粥样硬化患者中，我们使用高分辨率超声研究了8周口服氯沙坦治疗对肱动脉血流介导性血管舒张的影响。口服氯沙坦治疗改善了血流介导性肱动脉扩张（从1.4±0.9%至3.2±0.8%，P = 0.03），但对硝酸甘油反应无影响。血清一氧化氮水平从21.6±1.7微摩尔/升升至26.7±2.4微摩尔/升（P = 0.008）。
本研究结果表明，抑制动脉粥样硬化患者的AT(1)受体可通过改善一氧化氮的可用性来逆转内皮功能障碍，因此可能具有长期治疗益处。
