Lottermoser K, Ulrich-Merzenich G, Vetter H, Düsing R
Medizinische Universitäts-Poliklinik, Bonn.
Dtsch Med Wochenschr. 2003 Nov 21;128(47):2470-5. doi: 10.1055/s-2003-44318.
Inflammatory reactions mediated by cytokines play a central role in the development of atherosclerotic vascular changes. Numerous experimental studies have suggested a connection between the renin-angiotensin-aldosterone system and cytokine liberation from endothelium. This study investigated the effect of exogenous angiotensin II on cytokine liberation in healthy subjects.
Nine healthy men, aged 25-28 years, having given informed consent, were given angiotensin II infusions of 1, 3 and 10 ng/kg/min, each time over 45 min, once with and once without preceding oral intake of an AT (1)-receptor antagonist (160 mg valsartan). Arterial blood pressures were measured oscillometrically every 5 min. Blood was taken at the end of each perfusion period and one each after its end, measurements being made of plasma activity of angiotensin II, aldosterone, and the pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and the vascular cell adhesion molecule (VCAM)-1.
Plasma angiotensin II concentrations during perfusion rose from 14.7 +/- 16.5 pg/ml to 200.1 +/- 127.2 pg/ml (p< 0.001). The plasma concentrations of angiotensin II were again within the basal range (16.3 +/- 24.8 pg/ml) one hour after the end of perfusion. Angiotensin II raised the systolic and diastolic blood pressure from 121 +/- 9/70 +/- 6 mmHg to a maximum of 146 +/- 6/97 +/- 3 mmHg (p<0.001). This blood pressure rise was prevented by prior administration of the AT (1)-receptor antagonist. Neither the angiotensin II infusion nor the simultaneous administration of AT (1)-antagonist altered the circulating plasma level of TNF-alpha, IL-6 or VCAM-1.
Increased circulating plasma levels of angiotensin II induce a significant rise in arterial pressure of healthy male subjects, but do not in the short therm produce a change in the plasma levels of the cytokines TNF-alpha, IL-6 and VCAM-1. These results in healthy subjects throw doubt on the hypothesis that, at least in the short term, the effect of angiotensin II on changes in those cytokines measured in this study are independent of the blood pressure.
细胞因子介导的炎症反应在动脉粥样硬化血管病变的发展中起核心作用。众多实验研究表明肾素 - 血管紧张素 - 醛固酮系统与内皮细胞释放细胞因子之间存在联系。本研究调查了外源性血管紧张素II对健康受试者细胞因子释放的影响。
9名年龄在25 - 28岁之间且已签署知情同意书的健康男性，分别以1、3和10 ng/kg/min的速率输注血管紧张素II，每次持续45分钟，一次在口服AT（1）受体拮抗剂（160 mg缬沙坦）之前，一次在未口服之前。每5分钟通过示波法测量动脉血压。在每个灌注期结束时以及结束后各取一次血，检测血浆中血管紧张素II、醛固酮以及促炎细胞因子肿瘤坏死因子（TNF） - α、白细胞介素（IL） - 6和血管细胞粘附分子（VCAM） - 1的活性。
灌注期间血浆血管紧张素II浓度从14.7±16.5 pg/ml升至200.1±127.2 pg/ml（p<0.001）。灌注结束1小时后，血浆血管紧张素II浓度再次回到基础范围（16.3±24.8 pg/ml）。血管紧张素II使收缩压和舒张压从121±9/70±6 mmHg升至最高146±6/97±3 mmHg（p<0.001）。预先给予AT（1）受体拮抗剂可预防血压升高。血管紧张素II输注以及同时给予AT（1）拮抗剂均未改变循环血浆中TNF - α、IL - 6或VCAM - 1的水平。
循环血浆中血管紧张素II水平升高可使健康男性受试者的动脉血压显著升高，但短期内不会使细胞因子TNF - α、IL - 6和VCAM - 1的血浆水平发生变化。这些在健康受试者中的结果对以下假设提出了质疑：至少在短期内，血管紧张素II对本研究中所测细胞因子变化的影响与血压无关。
