Blanc J, Lambert G, Elghozi J L
Laboratoire de pharmacologie, CNRS UMR 8604, faculté de médecine Necker, Paris.
Arch Mal Coeur Vaiss. 2000 Aug;93(8):1019-22.
This study was designed to assay, using spectral analysis, the influence of the renin-angiotensin system activation on the blood pressure variability. Rats were surgically prepared with a supra-renal catheter inserted via the left carotid artery to perform local infusions and with a femoral artery catheter to measure blood pressure (BP) and heart rate (HR). The beta-adrenoceptors stimulation by isoprenaline was used to increase the plasma renin activity (PRA). A first group (n = 8) was infused with isoprenaline (0, 0.003, 10, 100, 300 ng/kg/min) at a rate of 20 microL/min. A second group (n = 8) received a bolus of the angiotensin II (AII) AT1 receptor-antagonist valsartan (2 mg/kg/mL, i.a.) prior to isoprenaline infusions. Five groups were used for blood sampling (one group infused with one concentration of isoprenaline) to assay PRA and catecholamines (CA). BP recordings were analysed using the fast Fourier transforms (FFT) on 2048 points time series (204.8 s). Isoprenaline from the concentration of 10 ng/kg/min increased PRA with a maximum effect of 8.5 fold with the highest concentration (300 ng/kg/min, p < 0.05); CA were not modified. Isoprenaline amplified the low-frequency (LF: 0.02-0.20 Hz) component of the systolic BP (SBP) variability (10 ng/kg/min: 4.16 +/- 0.62 mmHg2 versus: 2.90 +/- 0.44 mmHg2 for control value, p < 0.05) even if it did not modify BP and HR levels. Isoprenaline lowered BP and had a tachycardic effect at concentrations > or = 100 ng/kg/mL (at 100 ng/kg/mL: SBP = 115 +/- 3 mmHg, HR = 464 +/- 15 bpm, versus control: SBP = 128 +/- 3 mmHg, HR = 351 +/- 7 bpm, p < 0.05). Valsartan modified neither BP levels nor BP variability but exerted a tachycardic effect (+25 bpm, p < 0.001). Valsartan prevented the amplification of the LF oscillations of SBP induced by isoprenaline (10 ng/kg/min: 2.53 +/- 0.38 mmHg2 versus: 2.20 +/- 0.25 mmHg2 for control value (valsartan), ns). We conclude that a moderate endogenous production of renin increases SBP variability in the LF range in the conscious rat. This effect which does not affect BP and HR levels is mediated by AII AT1 receptors and does not involve the sympathetic nervous system.
本研究旨在通过频谱分析测定肾素 - 血管紧张素系统激活对血压变异性的影响。通过手术给大鼠经左颈动脉插入肾上腺导管以进行局部输注，并经股动脉插入导管以测量血压（BP）和心率（HR）。使用异丙肾上腺素刺激β - 肾上腺素能受体以增加血浆肾素活性（PRA）。第一组（n = 8）以20微升/分钟的速率输注异丙肾上腺素（0、0.003、10、100、300纳克/千克/分钟）。第二组（n = 8）在输注异丙肾上腺素之前先给予一剂血管紧张素II（AII）AT1受体拮抗剂缬沙坦（2毫克/千克/毫升，腹腔注射）。使用五组进行血液采样（一组输注一种浓度的异丙肾上腺素）以测定PRA和儿茶酚胺（CA）。对2048个时间点（204.8秒）的BP记录使用快速傅里叶变换（FFT）进行分析。浓度为10纳克/千克/分钟及以上的异丙肾上腺素可增加PRA，最高浓度（300纳克/千克/分钟）时最大效应为8.5倍（p < 0.05）；CA未发生改变。异丙肾上腺素放大了收缩压（SBP）变异性的低频（LF：0.02 - 0.20赫兹）成分（10纳克/千克/分钟时：4.16±0.62 mmHg²，而对照值为：2.90±0.44 mmHg²，p < 0.05），即便它未改变BP和HR水平。异丙肾上腺素在浓度≥100纳克/千克/毫升时可降低BP并产生心动过速效应（在100纳克/千克/毫升时：SBP = 115±3 mmHg，HR = 464±15次/分钟，而对照为：SBP = 128±3 mmHg，HR = 351±7次/分钟，p < 0.05）。缬沙坦既未改变BP水平也未改变BP变异性，但产生了心动过速效应（+25次/分钟，p < 0.001）。缬沙坦可防止异丙肾上腺素诱导的SBP低频振荡的放大（10纳克/千克/分钟时：2.53±0.38 mmHg²，而对照值（缬沙坦）为：2.20±0.25 mmHg²，无显著性差异）。我们得出结论，适度的内源性肾素产生会增加清醒大鼠LF范围内的SBP变异性。这种不影响BP和HR水平的效应由AII AT1受体介导，且不涉及交感神经系统。
