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

Cuixia Gao,Tingting Li,Qian Guo,Jing Liu,Limin Tian,Luis Eduardo M Quintas

doi:10.1371/journal.pone.0131776

Abstract

ObjectiveSubclinical 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.MethodsIn 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.kg-1.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.kg-1.d-1 L-T4 once daily by gavage after 45 days of MMI administration. The control rats received physiological saline via gavage.ResultsThe 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.ConclusionsThese findings demonstrate that L-T4 treatment ameliorates endothelial dysfunction and hemodynamic changes in SCH rats.

Highlights

Subclinical hypothyroidism (SCH), the mildest form of hypothyroidism, is defined by an increased concentration of thyroid-stimulating hormone (TSH) in the presence of a normal thyroid hormone concentration[1]
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 subclinical hypothyroid rats treated with L-T4 (SCH+T4) groups
Hemodynamic Parameters in Subclinical Hypothyroid Rats. These findings demonstrate that L-T4 treatment ameliorates endothelial dysfunction and hemodynamic changes in SCH rats

Summary

Introduction

Subclinical hypothyroidism (SCH), the mildest form of hypothyroidism, is defined by an increased concentration of thyroid-stimulating hormone (TSH) in the presence of a normal thyroid hormone concentration[1]. A growing body of evidence suggests that SCH has important clinical impacts on atherosclerosis (AS)[2, 3] and coronary endothelial dysfunction[4], leading to an increased risk of cardiovascular (CV) disease[5]. Previous studies have indicated that an abnormal TSH level is a risk factor for heart disease[6, 7]. TSH affects the heart rate[8], ventricular functioning and coronary artery disease risk [9]. Decreased NO generation of circulating concentrations is an early physiological event in AS and can be used as a prognostic factor for CV disease[13]. Previous studies have demonstrated that endothelial dysfunction has a negative prognostic impact on the long-term outcome of coronary heart disease[14, 15]. The crucial mechanism of this endothelial dysfunction remains unclear

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Conclusion