Grassi G, Turri C, Dell'Oro R, Stella M L, Bolla G B, Mancia G
Cattedra di Medicina Interna I, Ospedale S. Gerardo Monza, Università di Milano, Milan, Italy.
J Hypertens. 1998 Dec;16(12 Pt 1):1789-96. doi: 10.1097/00004872-199816120-00012.
Human studies have shown that the blood pressure lowering effects of angiotensin converting enzyme inhibitors are accompanied by a reduction in plasma norepinephrine levels. Whether this is due to central or peripheral mechanisms is unknown, however.
To evaluate the effects of chronic interference with the renin-angiotensin system on sympathetic nerve traffic and baroreflex control of vagal and adrenergic cardiovascular drive.
In 18 untreated mild to moderate essential hypertensive patients aged 48.5+/-1.9 years (mean+/-SEM), we measured mean arterial pressure (Finapres), heart rate (electrocardiogram), plasma renin activity (radioimmunoassay), plasma norepinephrine (high-performance liquid chromatography) and postganglionic muscle sympathetic nerve activity (microneurography at a peroneal nerve). In nine patients, measurements were performed before and after 2 months of oral administration of lisinopril (10 mg/day), while in the remaining nine patients they were performed before and after a 2 month observation period, without the drug administration. Measurements were performed at rest and during baroreflex stimulation and deactivation elicited by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively.
Lisinopril induced a marked increase in plasma renin activity (from 1.1+/-0.2 to 6.4+/-1.3 ng/ml per h, P< 0.01) and a reduction in mean arterial pressure (from 109.6+/-3.1 to 98.7+/-2.9 mmHg, P < 0.01) without affecting the heart rate. Plasma norepinephrine and muscle sympathetic nerve activity values were not significantly different before and after lisinopril treatment (plasma norepinephrine values changed from 290.4+/-39.2 to 308.1+/-67.1 pg/ml; muscle sympathetic nerve activity changed from 56.4+/-5.3 to 50.6+/-6.6 bursts/100 heart beats). Neither the sympathoinhibitory nor the sympathoexcitatory responses to phenylephrine and nitroprusside were affected by lisinopril, nor the concomitant bradycardia and tachycardia. The curves relating mean arterial pressure to heart rate and muscle sympathetic nerve activity values during baroreceptor manipulation were shifted to the left, indicating a resetting of the baroreflex to the lower blood pressure values achieved during treatment. CONCLUSIONS In essential hypertension, sympathetic nerve traffic is not affected by chronic angiotensin converting enzyme inhibitor treatment that effectively interferes with the renin-angiotensin system and lowers the elevated blood pressure. The baroreflex ability to modulate heart rate and central sympathetic outflow is also unaffected. These data argue against the existence of a central sympathoexcitatory effect of angiotensin II in this condition. They also indicate that antihypertensive treatment with an angiotensin converting enzyme inhibitor preserves autonomic reflex control, with favorable consequences for cardiovascular homeostasis.
人体研究表明，血管紧张素转换酶抑制剂的降压作用伴随着血浆去甲肾上腺素水平的降低。然而，这是由于中枢机制还是外周机制尚不清楚。
评估长期干扰肾素-血管紧张素系统对交感神经活动以及迷走神经和肾上腺素能心血管驱动的压力反射控制的影响。
在18例未经治疗的48.5±1.9岁（均值±标准误）的轻度至中度原发性高血压患者中，我们测量了平均动脉压（Finapres）、心率（心电图）、血浆肾素活性（放射免疫测定法）、血浆去甲肾上腺素（高效液相色谱法）以及节后肌肉交感神经活动（通过腓总神经的微神经ography）。9例患者在口服赖诺普利（10mg/天）2个月前后进行测量，而其余9例患者在2个月观察期前后进行测量，期间未给药。测量在静息状态下以及分别通过逐步静脉输注去氧肾上腺素和硝普钠引发的压力反射刺激和失活过程中进行。
赖诺普利使血浆肾素活性显著增加（从1.1±0.2至6.4±1.3ng/ml每小时，P<0.01），并使平均动脉压降低（从109.6±3.1至98.7±2.9mmHg，P<0.01），但不影响心率。赖诺普利治疗前后血浆去甲肾上腺素和肌肉交感神经活动值无显著差异（血浆去甲肾上腺素值从290.4±39.2变为308.1±67.1pg/ml；肌肉交感神经活动从56.4±5.3变为50.6±6.6次爆发/100次心跳）。赖诺普利既不影响对去氧肾上腺素和硝普钠的交感抑制反应也不影响交感兴奋反应，也不影响伴随的心动过缓和心动过速。在压力感受器操作期间，将平均动脉压与心率和肌肉交感神经活动值相关的曲线向左移动，表明压力反射已重置为治疗期间达到的较低血压值。结论在原发性高血压中，交感神经活动不受有效干扰肾素-血管紧张素系统并降低升高血压的慢性血管紧张素转换酶抑制剂治疗的影响。调节心率和中枢交感神经流出的压力反射能力也未受影响。这些数据反对在这种情况下血管紧张素II存在中枢交感兴奋作用。它们还表明用血管紧张素转换酶抑制剂进行的抗高血压治疗保留了自主反射控制，对心血管稳态有有利影响。
