Contribution of the renin-angiotensin system to short-term arterial pressure variability in hyperthyroid rats

Objectives: To produce a chronical thyrotoxicosis model in rat, and to eval uate, using spectral analysis, the involvement of the renin-angiotensin sys tem (RAS) in short-term variability of blood pressure (BP) in experimental hyperthyroidism. Design and methods: 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 so lvent. Two series of experiments were performed in conscious and unrestrain ed rats. In the first series, 10 euthyroid and 14 hyperthyroid rats were su rgically prepared with a femoral artery catheter to measure BP and heart ra te (HR) and to collect blood samples on the last day of treatment. In the s econd series of experiments (n=12 in each group), on the fifteenth day of t reatment, BP and HR were recorded by telemetry in control conditions and af ter a specific blockade of the RAS by the angiotensin type 1 receptors anta gonist: valsartan (10 mg/kg, i.p.). BP recordings were analysed by the Fast Fourier Transform on consecutive 204.8-s stationary periods. Results: The dose and duration of T4 treatment was sufficient to induce a s ignificant 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. Hyperthy roidism modified systolic BP (SBP) variability profiles. An amplification o f 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 dimi nished the slow fluctuations of SEP (p<0.001) and increased the mid-frequen cy oscillations (2.44+/-0.20 mmHg vs 1.32+/-0.18 mmHg, p<0.001). Conclusion: The cardiovascular alterations of hyperthyroidism are reproduce d with thyroid hormone injections in rats. Activation of the RAS in hyperth yroid rats was accompanied by increased SEP variability in the LF range. Us ing the angiotensin type I receptors antagonist, valsartan, we demonstrated that the RAS impinged on the LF oscillations of the SEP in our experimenta l hyperthyroidism model.