Endothelial Functioning and Hemodynamic Parameters in Rats with Subclinical Hypothyroid and the Effects of Thyroxine Replacement.

Abstract

OBJECTIVE: Subclinical hypothyroidism (SCH) and its associations with atherosclerosis (AS) and cardiovascular disease remain controversial. The purpose of our study was to observe changes in endothelial functioning and hemodynamics in rats with SCH and to determine whether L-thyroxine (L-T4) administration affects these changes. METHODS: In total, sixty male Wistar rats were randomly divided into the following three groups with 20 rats each: control euthyroid rats, SCH rats and SCH rats that had been treated with thyroxine (SCH+T4). The SCH rats were induced by administration of 10 mg x kg(-1) x d(-1) methimazole (MMI) once daily by gavage for 3 months. The SCH+T4 rats were administered the same dose of MMI for three months in addition to 2 μg x kg(-1) x d(-1) L-T4 once daily by gavage after 45 days of MMI administration. The control rats received physiological saline via gavage. RESULTS: The SCH group had significantly higher thyroid-stimulating hormone (TSH), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and endothelin (ET) levels and a lower nitric oxide (NO) level than the control and SCH+T4 groups. The tail and carotid artery blood pressures, left ventricular systolic pressure, heart rate and aorta ventralis blood flow were significantly lower in the SCH group than in the control and SCH+T4 groups. ACH treatment caused concentration-dependent relaxation, which was reduced in the SCH arteries compared with the control and SCH+T4 arteries. Histopathological examination revealed the absence of pathological changes in the SCH rat arteries. CONCLUSIONS: These findings demonstrate that L-T4 treatment ameliorates endothelial dysfunction and hemodynamic changes in SCH rats.