[Contribution of the renin-angiotensin system to blood pressure variability in hyperthyroid rats].
OBJECTIVE
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.


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 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.


RESULTS
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).


CONCLUSIONS
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.
Basset
A
A
Laboratoire de pharmacologie, CNRS UMR 8604, faculté de médecine Necker, Paris.
Blanc
J
J
Elghozi
J L
JL
D000803:Angiotensin I / Q000037:antagonists & inhibitors; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D006332:Cardiomegaly / Q000503:physiopathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D005334:Fever / Q000503:physiopathology; D005583:Fourier Analysis; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology; D006980:Hyperthyroidism / Q000097:blood / Q000503:physiopathology*; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D012815:Signal Processing, Computer-Assisted; D013610:Tachycardia / Q000503:physiopathology; D013777:Tetrazoles / Q000494:pharmacology; D013963:Thyroid Hormones / Q000097:blood; D013971:Thyrotoxicosis / Q000097:blood / Q000503:physiopathology; D013974:Thyroxine / Q000008:administration & dosage / Q000009:adverse effects; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan; D015431:Weight Loss / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D013777:Tetrazoles; D013963:Thyroid Hormones; D000068756:Valsartan; D000803:Angiotensin I; D012083:Renin; D014633:Valine; D013974:Thyroxine