Renin-angiotensin system contribution to cardiac hypertrophy in experimental hyperthyroidism: An echocardiographic study

The objective of this study was to evaluate, using echocardiography, the in volvement of the renin-angiotensin system (RAS) in left ventricular (LV) hy pertrophy development in experimental hyperthyroidism. Thyrotoxicosis was p roduced by a daily intraperitoneal injection of L-thyroxine (T-4), 0.1 mg/k g per day for 15 days in Wistar rats. Control (euthyroid) rats received int raperitoneal daily injection of the thyroxine solvent. Two series of experi ments were per formed. In the first series, euthyroid (n = 10) and hyperthy roid (n = 14) rats were surgically prepared with a femoral artery catheter. After a 3-day recovery period, blood pressure and heart rate were measured and blood samples were collected in conscious and unrestrained rats. In th e second series of experiment, measurement of LV geometry was realized with two-dimensional time-movement echocardiography on the 15th day of treatmen t in control conditions and after long-term treatment with the angiotensin II type 1 receptor antagonist valsartan (10 mg/kg per day for 15 days) in b oth euthyroid and hyperthyroid rats. The dose and duration of T-4 treatment was sufficient to induce a significant degree of hyperthyroidism with char acteristic features including tachycardia, systolic hypertension, myocardia l hypertrophy, hyperthermia, and weight loss. In addition, we measured an i ncrease in free fractions of thyroid hormones, and a threefold increase in plasma lenin activity. Echocardiographic examinations in rats revealed a st rong correlation between LV weight and echocardiographic LV mass. Hyperthyr oid rats exhibited an increased LV mass with a marked increase in the LV en d-diastolic posterior wall and septal thickness. Chronic treatment with val sartan prevented this concentric LV hypertrophy (p < 0.01), with full preve ntion of the LV posterior wall hypertrophy (p < 0.001) and decreased LV sep tal hypertrophy (p < 0.05). In conclusion, the cardiovascular alterations o f hyperthyroidism were reproduced with thyroid hormone injections in rats. Activation of the RAS in hyperthyroid rats was accompanied by increased LV mass. Using valsartan, we demonstrated that the RAS impinged on the LV remo delling in our experimental hyperthyroidism model. A chronic treatment with an angiotensin II type I receptor antagonist prevented the development of the concentric LV hypertrophy associated with thyrotoxicosis.