Endothelial Functioning And Hemodynamic Parameters In Rats With Subclinical Hypothyroid And The Effects Of Thyroxine Replacement

Objective: Hypothyroidism is well known to be associated with atherosclerosis(AS) and cardiovascular, and subclinical hypothyroidism(SCH) associations with AS and cardiac function remain controversial. Endothelial dysfunction has been implicated the first step in the development of AS. Similarly, the change of cardiac systolic and diastolic function have profound effects on cardiac structure and function. Whether levothyroxine(L-T4)replacement of SCH can reduce AS and cardiovascular events. 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 10mg·kg-1·d-1methimazole(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 2μg·kg-1·d-1L-T4 once daily by gavage after 45 days of MMI administration. The control rats received water via gavage. Determination of serum lipids, endothelin(ET), nitric oxide(NO) levels and monitoring the rat tail and carotid artery blood pressure, left ventricular function, abdominal aortic blood flow, vascular relaxation response and histopathological analysis of the arcus aorta.Results: The SCH group had significantly higher total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), and ET levels and a lower NO level than the control and SCH+T4 groups. The tail and carotid artery blood pressures, left ventricular systolic pressure,left ventricular end-diastolic pressure, minimal rate of pressure decline, maximal rate of pressure rise, heart rate and aorta ventralis blood flow were significantly decreased in the SCH group than in the control. SCH group time constant of left ventricular isovolumic relaxation and contractility Index is higher than the control group(P <0.05). L-T4 treatment can improves cardiac function index of SCH ratsConclusions: These findings demonstrate that L-T4 treatment ameliorates endothelial dysfunction and hemodynamic changes in SCH rats.