Basset A, Blanc J, Elghozi J L
Laboratoire de pharmacologie, CNRS UMR 8604, faculté de médecine Necker, Paris.
Arch Mal Coeur Vaiss. 2000 Aug;93(8):905-10.
To produce a chronical thyrotoxicosis model in rat, and to evaluate, using spectral analysis, the involvement of the renin-angiotensin system (RAS) in short-term variability of blood pressure (BP) in experimental hyperthyroidism.
Thyrotoxicosis was produced by a daily intraperitoneal (i.p.) injection of L-thyroxine (T4: 0.1 mg/kg for 15 days) in Wistar rats. Control (euthyroid) rats received i.p. daily injection of the thyroxine solvent. Two series of experiments were performed in conscious and unrestrained rats. In the first series, 10 euthyroid and 14 hyperthyroid rats were surgically prepared with a femoral artery catheter to measure BP and heart rate (HR) and to collect blood samples on the last day of treatment. In the second series of experiments (n = 12 in each group), on the fifteenth day of treatment, BP and HR were recorded by telemetry in control conditions and after a specific blockade of the RAS by the angiotensin type I receptors antagonist: valsartan (10 mg/kg, i.p.). BP recordings were analysed by the Fast Fourier Transform on consecutive 204.8-s stationary periods.
The dose and duration of T4 treatment was sufficient to induce a significant degree of hyperthyroidism with characteristic features including: tachycardia, systolic hypertension, myocardial hypertrophy, hyperthermia, and weight loss. In addition, we measured an increase in free fractions of thyroid hormones, and a 3 fold-increase of plasma renin activity. Hyperthyroidism modified systolic BP (SBP) variability profiles. An amplification of low frequency (LF) oscillations (2.37 +/- 0.12 mmHg vs 1.78 +/- 0.11 mmHg, p < 0.01) was observed after T4 treatment. In hyperthyroid rats, valsartan diminished the slow fluctuations of SBP (p < 0.001) and increased the mid-frequency oscillations (2.44 +/- 0.20 mmHg vs 1.32 +/- 0.18 mmHg, p < 0.001).
The cardiovascular alterations of hyperthyroidism are reproduced with thyroid hormone injections in rats. Activation of the RAS in hyperthyroid rats was accompanied by increased SBP variability in the LF range. Using the angiotensin type I receptors antagonist, valsartan, we demonstrated that the RAS impinged on the LF oscillations of the SBP in our experimental hyperthyroidism model.
建立大鼠慢性甲状腺毒症模型，并通过频谱分析评估肾素 - 血管紧张素系统（RAS）在实验性甲状腺功能亢进症中对血压（BP）短期变异性的影响。
通过每日腹腔注射L - 甲状腺素（T4：0.1mg/kg，共15天）在Wistar大鼠中诱导甲状腺毒症。对照（甲状腺功能正常）大鼠每日腹腔注射甲状腺素溶剂。在清醒且不受限制的大鼠中进行了两个系列的实验。在第一个系列中，10只甲状腺功能正常和14只甲状腺功能亢进的大鼠在治疗的最后一天通过手术植入股动脉导管以测量血压和心率（HR）并采集血样。在第二个系列实验中（每组n = 12），在治疗的第15天，通过遥测记录对照条件下以及在使用血管紧张素I型受体拮抗剂缬沙坦（10mg/kg，腹腔注射）特异性阻断RAS后的血压和心率。通过快速傅里叶变换对连续204.8秒的平稳期血压记录进行分析。
T4治疗的剂量和持续时间足以诱导显著程度的甲状腺功能亢进症，其特征包括：心动过速、收缩期高血压、心肌肥大、体温过高和体重减轻。此外，我们测量到甲状腺激素游离部分增加，血浆肾素活性增加了3倍。甲状腺功能亢进症改变了收缩压（SBP）变异性特征。T4治疗后观察到低频（LF）振荡放大（2.37±0.12mmHg对1.78±0.11mmHg，p < 0.01）。在甲状腺功能亢进的大鼠中，缬沙坦减少了SBP的缓慢波动（p < 0.001）并增加了中频振荡（2.44±0.20mmHg对1.32±0.18mmHg，p < 0.001）。
通过给大鼠注射甲状腺激素可再现甲状腺功能亢进症的心血管改变。甲状腺功能亢进大鼠中RAS的激活伴随着LF范围内SBP变异性增加。使用血管紧张素I型受体拮抗剂缬沙坦，我们证明在我们的实验性甲状腺功能亢进症模型中RAS影响SBP的LF振荡。
