Blanc J, Lambert G, Elghozi J L
Laboratoire de Pharmacologie, CNRS UMR 8604, Faculté de Médecine Necker, 156 rue de Vaugirard, 75015, Paris, France.
Eur J Pharmacol. 2000 Apr 14;394(2-3):311-20. doi: 10.1016/s0014-2999(00)00070-4.
This study was designed to investigate, by use of spectral analysis, the blood pressure variability changes induced in the conscious rat by activation of plasmatic renin activity. Rats were surgically prepared with a supra-renal catheter inserted via the left carotid artery to perform the infusions, and with a femoral artery catheter to measure blood pressure and heart rate. Secretion of renin was induced using beta-adrenoceptor stimulation produced by isoprenaline. A first group (n=8) was infused with isoprenaline: 0.003, 10, 100 and 300 ng/kg/min, at a rate of 20 microl/min. A second group (n=8) was given a bolus injection of the angiotensin AT(1) receptor antagonist, valsartan (2 mg/kg, i.a.), prior to isoprenaline infusions. The lack of effect of infusion per se was checked in additional animals (n=8) infused with saline only (20 microl/min). Five other groups of animals were prepared with arterial catheters as mentioned previously. Each group received one concentration of infused isoprenaline and samples of blood were collected for further determinations of plasma renin activity and catecholamine concentrations. Blood pressure recordings were analysed using the fast Fourier transform on 2048 points time series (204.8 s). Isoprenaline increased plasma renin activity and did not modify plasma catecholamine concentrations. The low-frequency (0.02-0.2 Hz) component of the systolic blood pressure variability was amplified by isoprenaline (10 ng/kg/min isoprenaline: 4.16+/-0.62 mm Hg(2) vs. 2.90+/-0.44 mm Hg(2) for control value, P<0.05), a concentration that did not alter either blood pressure or heart rate levels. Isoprenaline lowered blood pressure and increased heart rate, starting at concentrations of 100 ng/kg/min. Valsartan, whose principal effect was generation of tachycardia (+25 bpm) modified neither blood pressure levels nor blood pressure variability. Valsartan prevented the amplification of the low-frequency oscillations of systolic blood pressure induced by isoprenaline (10 ng/kg/min isoprenaline: 2.53+/-0.38 mm Hg(2) vs. 2.20+/-0.25 mm Hg(2) for control value (valsartan, ns). We conclude that a moderate increase of plasma renin activity enhanced systolic blood pressure variability in the low-frequency range, without affecting blood pressure and heart rate levels.
本研究旨在通过频谱分析，研究激活血浆肾素活性在清醒大鼠中引起的血压变异性变化。通过手术给大鼠经左颈动脉插入肾上腺导管以进行输注，并经股动脉导管测量血压和心率。使用异丙肾上腺素产生的β-肾上腺素能受体刺激诱导肾素分泌。第一组（n = 8）以20微升/分钟的速率输注异丙肾上腺素：0.003、10、100和300纳克/千克/分钟。第二组（n = 8）在输注异丙肾上腺素之前给予血管紧张素AT（1）受体拮抗剂缬沙坦（2毫克/千克，腹腔注射）。在仅输注生理盐水（20微升/分钟）的另外的动物（n = 8）中检查输注本身的无效应。如前所述，另外制备五组带有动脉导管的动物。每组接受一种浓度的输注异丙肾上腺素，并采集血样以进一步测定血浆肾素活性和儿茶酚胺浓度。使用快速傅里叶变换对2048个时间点（204.8秒）的血压记录进行分析。异丙肾上腺素增加血浆肾素活性，并且不改变血浆儿茶酚胺浓度。异丙肾上腺素（10纳克/千克/分钟异丙肾上腺素：4.16±0.62毫米汞柱²，而对照值为2.90±0.44毫米汞柱²，P<0.05）放大了收缩压变异性的低频（0.02 - 0.2赫兹）成分，该浓度既不改变血压也不改变心率水平。从100纳克/千克/分钟的浓度开始，异丙肾上腺素降低血压并增加心率。缬沙坦的主要作用是引起心动过速（+25次/分钟），既不改变血压水平也不改变血压变异性。缬沙坦阻止了异丙肾上腺素诱导的收缩压低频振荡的放大（10纳克/千克/分钟异丙肾上腺素：2.53±0.38毫米汞柱²，而对照值（缬沙坦，无显著性差异）为2.20±0.25毫米汞柱²）。我们得出结论，血浆肾素活性的适度增加增强了低频范围内的收缩压变异性，而不影响血压和心率水平。
