Table 2 shows macroscopic and histologic data of heart changes at the end of follow-up. Heart/body weight ratio increased in rats of the 5/6Nx when compared to animals in the control group. T4 supplementation partially prevented this increment. Heart/body weight ratio tended to be lower in Tx

rats. The left ventricle wall was thicker in 5/6Nx rats than in the control group or in the T4 supplemented animals. In the Tx group this variable also increased but to a different extent compared with 5/6Nx rats. Fibrosis measured by light histology as well as by hydroxyproline content was higher in the 5/6Nx rats compared with controls (Table 2, Figure 1). As in other aforementioned variables, T4 treatment significantly Selleck Navitoclax Selleckchem PF 2341066 prevented fibrosis. Tx animals also showed an increase in fibrosis, but to a lesser extent than in 5/6Nx groups. Immunostained areas for TGF-β were greater in the 5/6Nx rats than in either controls or T4-treated animals (Table 2, Figure 2). TGF-β was increased

in Tx rats, but it was below those values seen in 5/6Nx rats. Collagenase activity as measured by zymography was similar in all groups. Table 3 shows the gene expression of α- and β-MHC, which increased in 5/6Nx rats and slightly decreased in the Tx group when compared to the control group. TGF-β gene expression changed in the same way and follows results observed by immunohistochemistry. Expression of mir-208 decreased in 5/6Nx groups, and levels were restored with T4 supplementation. Data herein reported support the concept of low thyroid hormone levels as an important factor in the pathophysiology of hypertrophy and fibrosis

of the myocardium of rats with experimentally induced CKD and that mir-208 mediates hormone action. Appropriate interpretation of these results needs to consider several important aspects. The first is the model: 5/6Nx generates a moderate degree of CKD and not severe (as stage 5 may be in humans) renal failure. Etomidate The second important aspect refers to the degree of the effect of CKD on thyroid hormone levels. In humans, changes in thyroid hormones are associated with the severity of the primary disease and comprise a broad spectrum of variations, which can range from low-normal or slightly low levels in free T3 to severe drops in free and total T3 and T4 with elevated TSH (28). In this context, the model we analyzed was limited to moderate CKD and moderate changes in thyroid hormones. The third aspect to be considered in the interpretation of the results concerns other previously reported models to study the effects of thyroid hormones on the heart. These models have involved drastic changes in thyroid hormones, which are achieved through total thyroidectomy or the use of high doses of propylthiouracil (PTU) in the case of hypothyroidism or the administration of excessive doses of T3 or T4 for the study of hyperthyroidism.