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      Short-Term Thyroid Hormone Excess Affects the Heart but Does not Affect Adrenal Activity in Rats

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          Abstract

          Background

          Hyperthyroidism (Hy) exerts a broad range of influences on a variety of physiological parameters. Its disruptive effect on cardiovascular system is one of its most remarkable impacts. Moreover, Hy has been clinically associated with stress - induced hyperactivation of the hypothalamic-pituitary-adrenal axis.

          Objective

          Evaluate the impact of short-term Hy on cardiac performance and adrenal activity of rats.

          Methods

          Induction of Hy in Wistar rats through injections of T3 (150 µg/kg) for 10 days (hyperthyroid group - HG) or vehicle (control group). The cardiovascular performance was evaluated by: echocardiography (ECHO); heart weight/body weight (mg/gr) ratio; contractility of isolated papillary muscles (IPM) and direct measurement of blood pressures. Adrenal activity was evaluated by adrenal weight/body weight (mg/gr) ratio and 24-hour fecal corticosterone (FC) levels on the, 5 th and 10 th days of T3 treatment.

          Results

          In HG, the ECHO showed reduction of the End Systolic and End Diastolic Volumes, Ejection, Total Diastolic and Isovolumic Relaxation Times, Diastolic and Systolic Areas and E/A ratio. Heart Rate, Ejection Fraction and Cardiac Output increased. The heart weight/body weight ratio was higher. Similarly, in IPM, the maximum rate of force decay during relaxation was higher in all extracellular calcium concentrations. Systolic blood pressure (SBP) levels were higher. (p ≤ 0.05). On the other hand, there was no difference in the adrenal weight/body weight ratio or in the 24-hour FC levels.

          Conclusions

          Hy induces positive inotropic, chronotropic and lusitropic effects on the heart by direct effects of T3 and increases SBP. Those alterations are not correlated with changes in the adrenal activity.

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          Thyroid disease and the heart.

          The cardiovascular signs and symptoms of thyroid disease are some of the most profound and clinically relevant findings that accompany both hyperthyroidism and hypothyroidism. On the basis of the understanding of the cellular mechanisms of thyroid hormone action on the heart and cardiovascular system, it is possible to explain the changes in cardiac output, cardiac contractility, blood pressure, vascular resistance, and rhythm disturbances that result from thyroid dysfunction. The importance of the recognition of the effects of thyroid disease on the heart also derives from the observation that restoration of normal thyroid function most often reverses the abnormal cardiovascular hemodynamics. In the present review, we discuss the appropriate thyroid function tests to establish a suspected diagnosis as well as the treatment modalities necessary to restore patients to a euthyroid state. We also review the alterations in thyroid hormone metabolism that accompany chronic congestive heart failure and the approach to the management of patients with amiodarone-induced alterations in thyroid function tests.
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            Effects of sex and time of day on metabolism and excretion of corticosterone in urine and feces of mice.

            Non-invasive techniques to monitor stress hormones in small animals like mice offer several advantages and are highly demanded in laboratory as well as in field research. Since knowledge about the species-specific metabolism and excretion of glucocorticoids is essential to develop such a technique, we conducted radiometabolism studies in mice (Mus musculus f. domesticus, strain C57BL/6J). Each mouse was injected intraperitoneally with 740 kBq of 3H-labelled corticosterone and all voided urine and fecal samples were collected for five days. In a first experiment 16 animals (eight of each sex) received the injection at 9 a.m., while eight mice (four of each sex) were injected at 9 p.m. in a second experiment. In both experiments radioactive metabolites were recovered predominantly in the feces, although males excreted significantly higher proportions via the feces (about 73%) than females (about 53%). Peak radioactivity in the urine was detected within about 2h after injection, while in the feces peak concentrations were observed later (depending on the time of injection: about 10h postinjection in experiment 1 and about 4h postinjection in experiment 2, thus proving an effect of the time of day). The number and relative abundance of fecal [3H]corticosterone metabolites was determined by high performance liquid chromatography (HPLC). The HPLC separations revealed that corticosterone was extensively metabolized mainly to more polar substances. Regarding the types of metabolites formed, significant differences were found between males and females, but not between the experiments. Additionally, the immunoreactivity of these metabolites was assessed by screening the HPLC fractions with four enzyme immunoassays (EIA). However, only a newly established EIA for 5alpha-pregnane-3beta,11beta,21-triol-20-one (measuring corticosterone metabolites with a 5alpha-3beta,11beta-diol structure) detected several peaks of radioactive metabolites with high intensity in both sexes, while the other EIAs showed only minor immunoreactivity. Thus, our study for the first time provides substantial information about metabolism and excretion of corticosterone in urine and feces of mice and is the first demonstrating a significant impact of the animals' sex and the time of day. Based on these data it should be possible to monitor adrenocortical activity non-invasively in this species by measuring fecal corticosterone metabolites with the newly developed EIA. Since mice are extensively used in research world-wide, this could open new perspectives in various fields from ecology to behavioral endocrinology. Copyright 2003 Elsevier Science (USA)
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              Thyroid hormone action in the heart.

              The heart is a major target organ for thyroid hormone action, and marked changes occur in cardiac function in patients with hypo- or hyperthyroidism. T(3)-induced changes in cardiac function can result from direct or indirect T(3) effects. Direct effects result from T(3) action in the heart itself and are mediated by nuclear or extranuclear mechanisms. Extranuclear T(3) effects, which occur independent of nuclear T(3) receptor binding and increases in protein synthesis, influence primarily the transport of amino acids, sugars, and calcium across the cell membrane. Nuclear T(3) effects are mediated by the binding of T(3) to specific nuclear receptor proteins, which results in increased transcription of T(3)-responsive cardiac genes. The T(3) receptor is a member of the ligand-activated transcription factor family and is encoded by cellular erythroblastosis A (c-erb A) genes. T(3) also leads to an increase in the speed of diastolic relaxation, which is caused by the more efficient pumping of the calcium ATPase of the sarcoplasmic reticulum. This T(3) effect results from T(3)-induced increases in the level of the mRNA coding for the sarcoplasmic reticulum calcium ATPase protein, leading to an increased number of calcium ATPase pump units in the sarcoplasmic reticulum.
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                Author and article information

                Journal
                Arq Bras Cardiol
                Arq. Bras. Cardiol
                Arq. Bras. Cardiol.
                Arquivos brasileiros de cardiologia
                Sociedade Brasileira de Cardiologia
                0066-782X
                1678-4170
                March 2014
                : 102
                : 3
                : 270-278
                Affiliations
                [1 ] Universidade Federal do Paraná, Curitiba, PR -Brazil
                [2 ] Pontifícia Universidade Federal do Paraná, Curitiba, PR - Brazil
                [3 ] Universidade Federal da Bahia, Salvador, BA - Brazil
                Author notes
                Mailing Address: Ariani Cavazzani Szkudlarek. Alameda Prudente de Moraes, 732, apto. 54, Centro. Postal Code 80430-220, Curitiba, PR - Brazil. E-mail: arianiinaira@ 123456yahoo.com.br
                Article
                10.5935/abc.20140014
                3987310
                24676225
                20b5a724-b676-43a6-9242-c8b3670fd25c

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 June 2013
                : 12 August 2013
                : 19 September 2013
                Categories
                Original Articles

                thyroid hormones,hyperthyroidism / complications,adrenal glands,rats,cardiovascular diseases

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