© 1997 by European Society of Cardiology
Copyright © 1997, European Society of Cardiology
Thyroid hormones increase the contractility but suppress the effects of β-adrenergic agonist by decreasing phospholamban expression in rat atria
aDepartment of Pathophysiology, University of Tartu, EE2400 Tartu, Estonia
bMax Delbrück Center for Molecular Medicine, Berlin, D-13122 Berlin, Germany
* Corresponding author. Tel.: +372 (7) 465 295; fax: +372 (7) 465 298; e-mail: enn@ut.ee
Received 19 September 1996; accepted 24 January 1997
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Abstract |
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Objective: The aim of the present study was to characterize the relationships between the thyroid-hormone-dependent changes in sarcoplasmic reticulum (SR) Ca2+ handling and contractile performance in atria. Methods: Hypothyroidism in rats was induced by adding 0.05% 6-n-propyl-2-thiouracil to their drinking water for 6 weeks. Hyperthyroidism was induced by daily subcutaneous injections of L-thyroxine (1 µg/g body weight) to euthyroid rats for 1 week. Left atria from the hearts with different thyroid states were examined by means of contractile measurements, SR oxalate-supported Ca2+-uptake, and Western blot of SR proteins. Results: The tissue level of SR Ca2+-pump protein decreased in hypothyroid (46±6%) atria, but remained unchanged in hyperthyroid (110±8%) atria as compared with euthyroid atria. Hypothyroidism was associated with increased phospholamban expression (141±25%), whereas it was drastically downregulated under hyperthyroidism (21±4%). The rate of SR Ca2+-uptake, measured in the presence of the protein kinase A inhibitor, H-89, was higher in hyperthyroid atria and lower in hypothyroid atria than in euthyroid atria (397±40, 55±6 and 194±17 nmol Ca2+/g protein/min, respectively). However, the stimulation of SR Ca2+-uptake by the catalytic subunit of protein kinase A was relatively weaker in hyperthyroid (130±20% over control level without catalytic subunit) and stronger in hypothyroid (640±60%) than in euthyroid atria (280±40%). The rates of inotropic contraction (+dT/dt) were higher in the hyperthyroid atria (133±10 mN/s), but lower in hypothyroid atria (15±3 mN/s) than in their euthyroid counterparts (95±13 mN/s). Inversely, hypothyroid atria responded to isoproterenol with much larger increases in contractility (883±164% over the control values for the same muscle before addition of isoproterenol) and hyperthyroid with smaller increases (25±9%) than euthyroid preparations (207±17%). Conclusions: Thyroid hormones increase the contractility, but decrease the inotropic response to isoproterenol through decreasing the phospholamban/SR Ca2+-pump ratio in rat atria.
KEYWORDS Phospholamban; Thyroid hormone; SR Ca2+-ATPase; Isoproterenol; Contractile function; Rat, atrium
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1 Introduction |
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TopAbstract1 Introduction2 Methods3 Results4 DiscussionReferences |
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It is known that thyroid hormones increase cardiac output by augmenting systolic pressure development (+dP/dt) and fall (–dP/dt) combined with increased venous return [1–3]. The underlying molecular mechanisms have been well characterized in ventricular myocardium. Enhanced systolic pressure development (+dP/dt) has been attributed to hypertrophy of cardiomyocytes and stimulation of the expression of fast myosin isoenzyme (type V1) [2, 4]. On the other hand, increased expression of sarcoplasmic reticulum (SR) Ca2+-pump and suppression of its regulator, phospholamban, have been related to an enhanced rate of relaxation (–dP/dt) and a decreased lusitropic response to β-adrenergic agonists [5, 6].
The atrial contraction, by increasing the end-diastolic volume of blood, significantly contributes to ventricular stroke volume and systolic pressure [7]. This appears from the finding that loss of atrial systole due to atrial fibrillation manifests in a decline in left ventricular end-diastolic pressure [7]. In comparison with euthyroid or hypothyroid states, hyperthyroidism is characterized by increased overall chamber stiffness due to myocardial hypertrophy [1]. However, the stroke volume is increased and mean atrial pressure is unaffected [1]. These findings suggest that the atrial systole must strengthen in order to sustain the increased stroke volume despite the increased chamber stiffness. However, in contrast to ventricles, the pathophysiological changes and underlying molecular mechanisms in atria with altered thyroid state have been insufficiently studied. In particular, the effects of thyroid hormones on atrial SR Ca2+-pumping function, as well as the mechanisms of regulation of the SR Ca2+-pump by catecholamines, have not yet been assessed. Therefore, the aim of the current study was to estimate the effects of hypothyroidism and hyperthyroidism on oxalate-supported Ca2+-uptake in the presence and absence of protein kinase A (PKA) and the levels of SR Ca2+-pump and phopholamban proteins in rat atria. It is known that, in contrast to ventricles, the expression of myosin isoforms is almost insensitive to thyroid hormones in atria [8–10]. This allows elimination of interference of the changes in the myosin isoenzyme profile and thus specifically outline the role of altered SR function in governing contractility under varied thyroid states. Therefore, the effects of the thyroid state on basal contractile parameters and on the inotropic and lusitropic effects of isoproterenol (ISO) were assessed in relation to changes in expression of SR proteins. The results show that thyroid hormones increase the contractility and relaxation, but decrease the inotropic and lusitropic effects of ISO due to a decreased phospholamban/SR Ca2+-pump ratio in rat atria.
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2 Methods |
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TopAbstract1 Introduction2 Methods3 Results4 DiscussionReferences |
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2.1 Animals
White adult Wistar rats of both sexes, originally weighing 180–230 g, were made hypothyroid by adding 0.05% 6-n-propyl-2-thiouracil (Sigma Chemical Co.) to their drinking water for 6 weeks. Hyperthyroidism was induced by daily subcutaneous injections of L-thyroxine (Sigma Chemical Co.) to euthyroid animals, in a dose of 1 µg/g body weight for 1 week. The investigation conforms with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85-23, revised 1985).
2.2 Muscle preparation
The rats were anaesthetized with sodium thiopental, the hearts were removed, rinsed and the left atria were dissected in the medium that consisted of (in mM): NaCl 120, KCl 5.4, CaCl2 0.6, NaH2PO4 0.42, MgCl2 1.05, D-glucose 11, Na2-EDTA 0.05, 2,3-butanedione-monoxime 30, HEPES 5.0 (pH 7.4, 22°C) gassed with 100% O2. The atria were inserted into a 0.2 ml perfusion chamber between a force transducer and a length adjustment device. The perfusion medium, that contained (in mM) NaCl 120, KCl 5.4, CaCl2 1.0, NaH2PO4 0.42, MgCl2 1.05, D-glucose 11, Na2-EDTA 0.05, HEPES 5.0 (pH 7.4, 30°C), was gassed with 100% O2, and continuously circulated at a rate of 3–5 ml/min. The muscles were paced to contract by field-stimulation through two platinum electrodes placed parallel to the long axis of the preparation. The voltage stimulus (ranging from 5 to 15 V) was 1.5-fold that of the threshold value, and the duration and frequency of the rectangular pulse were 5 ms and 1 Hz, respectively. The output signals were amplified, recorded and analysed with an on-line personal computer using software ATRIUM, designed in our laboratory, to obtain the indices of isometric contraction.
2.3 Contractile studies
During the adaptation period, the muscle preparations were perfused without recirculation and stretched stepwise to the length at which the maximal isometric tension was achieved. After 45 min, the perfusion medium was switched to recirculate, and the muscles were allowed to adapt for another 15 min before 1 µM ISO was added. The contraction parameters were registered prior to and 5 min after ISO addition.
2.4 Preparation of atrial homogenates
The rats were anaesthetized with sodium thiopental and the hearts were excised and rinsed rapidly in ice-cold isotonic saline solution. The atria were isolated and weighed. All subsequent procedures were carried out at 4°C. Preparations were homogenized (3x30 s, 24 000 rpm) with Ultra-Thurrax (Janke and Kunkel, Germany) in 19 volumes of ice-cold buffer containing (in mM): sucrose 250, Tris 20 (pH 6.8), leupeptin 0.01, phenylmethylsulfonyl fluoride 0.1, dithiothreitol 1. The homogenates were further treated with glass-glass homogenizer (10 strokes).
2.5 Oxalate-supported Ca2+ uptake
The samples of atrial homogenate (30 µl) were incubated for 5 min at 30°C with constant shaking in the medium (in mM): ATP 2, MgCl2 2, KCl 100, NaN3 2, imidazole 30 (pH 7.0), K2-oxalate 2, and 14.4 µg/ml catalytic subunit of protein kinase A (specific activity 600 picomolar units/µg) or 100 µM H-89, a protein kinase A inhibitor (Biomol, USA). After the incubation period, the Ca2+ uptake was started by addition of 45Ca2+-labeled (Amersham, UK) CaCl2-EGTA buffer containing 580 µM EGTA and 117 µM of CaCl2 to give the free Ca2+ concentration 0.1 µM. After 3 min, the samples were filtered through Whatman glass microfibre filters GF/A by using a vacuum pump. Radioactivity associated with the membranes was counted in Optiphase ‘HiSafe’ 3 (Wallac, Finland).
2.6 Western blotting
The homogenates (100 µg of protein) were solubilized for 30 min at room temperature in 1.5% SDS, 62.5 mM Tris-HCl (pH 6.8), 7.5% glycerol, 3.8% mercaptoethanol, 0.0005% pyronin, 0.04% bromophenol blue, and proteins were separated by electrophoresis in SDS-polyacrylamide gels (total monomer concentration 7.6%, crosslinking monomer concentration 2.67%). The standard Laemmli protocol [11]was modified by including 4 M urea in the gels. Proteins were transferred to nitrocellulose membrane BA 85 (Schleicher and Schuell, Dassel, Germany) for 1.1 h at a constant voltage of 100 V at 4°C using a Minitransblot cell (Bio-Rad Laboratories, Richmond, CA) as described earlier [12]. This membrane was cut into two parts. Both parts were blocked for 1.5 h at room temperature in Tris-buffered saline containing Tween (TBS-T) [10 mM Tris-HCl (pH 7.4), 150 mM NaCl, 0.05% Tween 20] with 3% ovalbumin. Three subsequent washes of 10 min, each in TBS-T, were performed prior to the addition of antibodies. Membranes (upper part) for detecting the SR Ca2+-pump were first incubated with rabbit anti-SERCA2a antiserum (dilution 1:5000) for 1.5 h at room temperature in detergent-free TBS [50 mM Tris-HCl (pH 7.4), 120 mM NaCl] containing 1% bovine serum albumin and 0.04% NaN3. They were then washed twice for 10 min in TBS-T followed by 5 min in TBS-T with 3% ovalbumin and finally twice for 5 min in TBS. The membranes were incubated for 1 h with goat anti-rabbit IgG-horseradish peroxidase conjugate (1:4000 in TBS with 0.1% ovalbumin) and washed twice for 10 min in TBS-T and TBS, respectively. Membranes (lower part of the blot) for phospholamban were treated by the same procedures. However, a monoclonal mouse anti-phospholamban antibody (0.4 mg/ml) and anti-mouse IgG–horseradish peroxidase conjugate were used as the primary and secondary antibodies, respectively. Immunoreactive SERCA2a and phospholamban were visualized using an enhanced chemoluminescence analysis kit (ECL; Amersham, Little Chalfont, UK) and Kodak X-OMAT AR X-ray film. Exposure time was 1 min. The optical density of the immunoreactive bands was quantitated after densitometric scanning using a PDI scanner (Model DNA 35; PDI, Huntington Station, NY). Distinct amounts of protein (1–10 µg/lane) were used to check the linearity between the amount of protein applied and the intensity of the optical signal. The value of that parameter was considered to reflect the relative amounts of SERCA2a and phospholamban. Protein concentration was determined by the method of Lowry [13]using ovalbumin as a standard.
2.7 Statistical analysis
Data are presented as mean±s.e.m. Statistical significance was reached when P<0.05. Linear regression analysis was performed to determine the relationships between the contraction and relaxation rates and between the contraction parameters and phospholamban/SR Ca2+-pump ratio. The protein expression, SR Ca2+-uptake and contractile parameters of atria from different groups were compared using one-way ANOVA.
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3 Results |
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TopAbstract1 Introduction2 Methods3 Results4 DiscussionReferences |
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3.1 Effect of ISO on contraction parameters of rat atria
In this study, care was taken to minimize the influence of endogenous catecholamines on atrial contractile indices. Therefore, throughout the first 45 min of the adaptation period, the atria were perfused without recirculation of the medium. Under these conditions, the decrease in developed tension was observed which was considered to indicate the washout of catecholamines from the atrial preparations. By the end of the 45 min period, all muscles reached a stable plateau phase. Thereafter, the medium was switched to recirculate, and the atria were left to contract for the rest of the adaptation period (15 min) before the basal contractile indices were recorded.
Table 1 shows that, in comparison with the euthyroid state, hypothyroidism was associated with decreases in atrial contractility (+dT/dt), relaxation (–dT/dt), and developed tension (DT), whereas hyperthyroidism increased these parameters. Consequently, a shift from hypothyroid to hyperthyroid state was accompanied by a 9-fold and parallel increase in both contractility and relaxation (Fig. 1, Table 1).
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), hypothyroid (
) and hyperthyroid (
) rats. The linear relation is given by the regression line –dT/dt=0.73 (+dT/dt) +0.6 (r = 0.99, P<0.001).Fig. 2 shows the original recordings from atrial preparations before and after administration of ISO at a concentration of 1 µM. This concentration was chosen because it was the lowest one which caused a maximal response in hypothyroid group (data not shown). The data collected show that the effect of ISO on contractility was significantly higher in hypothyroid atria (883±164% over the control value for the same muscle before addition of ISO) and lower in hyperthyroid atria (25±9%) than in euthyroid ones (207±17%). Likewise, relaxation increased more in hypothyroid (798±132%) than in hyperthyroid atria (21±9%) in comparison with euthyroid preparations (188±10%). Thus, thyroid hormones, although accelerating atrial contractility and relaxation, decreased the responses of those parameters to ISO.
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3.2 Oxalate-supported SR Ca2+-uptake
To study the relationships between the changes in atrial contractile and SR functions, the oxalate-supported Ca2+-uptake in homogenates with different thyroid states was estimated in the presence of either the catalytic subunit of PKA or the inhibitor of PKA (H-89, 100 µM). Under the conditions of these experiments (see Section 2), Ca2+-uptake is restricted to SR, and therefore can be considered as the intrinsic SR Ca2+-uptake [14]. In the presence of H-89 which blocks endogenous PKA, the Ca2+-uptake rates were higher in hyperthyroid and lower in hypothyroid atria than in euthyroid preparations (Table 2). This fairly corresponds to thyroid-state-dependent changes in contractility and relaxation (Table 1, Fig. 1). Preincubation of atrial homogenates with 14.4 µg/ml catalytic subunit of PKA (the maximal effective concentration) led to increased rates of oxalate-supported Ca2+-uptake in all groups. However, compared to the euthyroid group, stimulation was relatively stronger in hypothyroid and weaker in hyperthyroid atria (Table 2), which corresponds to the effects of ISO on the contractile parameters (Table 1, Fig. 2).
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3.3 Immunoreactive protein levels of phospholamban and SR Ca2+-pump
To assess whether the thyroid hormone-dependent changes in SR function could be due to alterations in expression of SR Ca2+-pump and phospholamban in atria, the relative amounts of these proteins were determined by quantitative immunoblotting. In comparison with euthyroid atria, the expression of SR Ca2+-pump protein was suppressed, but expression of phospholamban increased in hypothyroid group (Fig. 3). In contrast, hyperthyroid atria showed a significantly decreased phospholamban expression together with unchanged SR Ca2+-pump. Consequently, the atrial relative phospholamban/SR Ca2+-pump ratio decreased 14-fold within a shift from hypothyroid to hyperthyroid state.
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3.4 Specific activity of SR Ca2+-pump
The ratios of the SR Ca2+-pump activity normalized to the optical density of immunoreactive bands may be considered to be linearly related to the specific activity of the SR Ca2+-pump. Therefore, these ratios were taken to index the specific SR Ca2+-pumping activity under different thyroid states. Fig. 4 suggests that in the presence of H-89 the specific activity of the Ca2+-pump increased in the direction from hypothyroid to hyperthyroid. However, this parameter was not different between all the groups studied in the presence of PKA.
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3.5 Relationship between contraction parameters and the phospholamban/SR Ca2+-pump ratio
Fig. 5A shows that in response to a shift from hypothyroid to hyperthyroid state, the decreases in relative phospholamban/SR Ca2+-pump ratio were accompanied by simultaneous increases in basal contractility and relaxation. At the same time, however, the extent of stimulation of these parameters by ISO decreased (Fig. 5B). Thus, thyroid hormones increased the contractility and relaxation, but suppressed their response to ISO through the common mechanism—by decreasing the phospholamban/SR Ca2+-pump ratio.
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) rats. Linear regression analysis revealed values of r
0.99 for all dependencies shown in A and B. Note that relative values of the phospholamban/SR Ca2+-pump ratio do not reflect the molar stoichiometries of these proteins. |
4 Discussion |
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TopAbstract1 Introduction2 Methods3 Results4 DiscussionReferences |
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This study confirms the results previously presented by Kiss et al. [6]and Beekman et al. [5]in that the thyroid-hormone-dependent alterations in the phospholamban/SR Ca2+-pump ratio are associated with changes in both basal relaxation and lusitropic response to ISO. However, the present study is the first to demonstrate that thyroid hormones exert control over contractility and its responses to ISO via changes in expression of these SR proteins in rat atria.
Comparisons of the muscles from different species have revealed a tight positive correlation between myosin ATPase activity and contractility [15]. On the other hand, in ventricular myocardium, the shift from the hypothyroid to the hyperthyroid state is associated with activation of expression of V1 myosin isoenzyme and suppression of V3 isoenzyme [8–10]. Based on these findings, it is generally believed that changes in the myosin ATPase isoenzyme profile underlie the increased cardiac contractility under thyroid hormones [5, 6]. Our results disagree with that theory because, although thyroid hormones did not affect myosin expression in atria [8–10], they caused a 9-fold increase in atrial +dT/dt (Table 1). Moreover, a reciprocal relationship was observed between the thyroid-hormone-dependent changes in +dT/dt and phospholamban/SR Ca2+-pump ratio (Fig. 5). These findings show that the changes in basal atrial contractility registered cannot be explained solely by changes in the myosin ATPase isoenzyme profile. Instead, Fig. 1 and Fig. 5A show that contractility is governed by the same mechanism as relaxation: that is, through changes in SR Ca2+ pump function which, in turn, is controlled by the inhibitory influence of phospholamban (Fig. 4). It appears that thyroid hormones modulate that mechanism by increasing the expression of the SR Ca2+-pump and suppressing the expression of phospholamban (Fig. 3). These changes result in faster accumulation of Ca2+, which possibly increases the extent of SR filling. In turn, the latter can provide more Ca2+ for release and, hence, increase contractility. Obviously, this mechanism of thyroid hormones action may play an important role in regulating ventricular contractility as well.
Fig. 2 shows that perfusion of hypothyroid atria with ISO led to almost a 10-fold enhancement of contractility and relaxation. Compared to hypothyroid atria, the effect of ISO was less expressed in euthyroid ones, whereas it was either minute or even lacking in hyperthyroid atria. It is known that the number of β-adrenoreceptors and sensitivity to ISO increase in the sequence hypothyroid<euthyroid<hyperthyroid atria [16, 17]. Furthermore, hypothyroid atria express less Gs protein than hyperthyroid ones [18]. These facts rule out the possibility that the observed large response of hypothyroid atria to ISO could be due to increased stimulation of adenylate cyclase. Most likely the thyroid-hormone-dependent alterations in inotropic response to ISO are based on changes in expression of phospholamban [5, 6]. This is supported by the finding that the increased response of hypothyroid atria to ISO (Fig. 2) was associated with a larger stimulation of oxalate-supported Ca2+-uptake by PKA (Table 2) and with an increased phospholamban/SR Ca2+-pump ratio (Fig. 3), while the decreased response of hyperthyroid atria was associated with opposite changes. Thus, due to the higher phospholamban content, in hypothyroid atria SR function was more upregulated by ISO-dependent phosphorylation of phospholamban than in hyperthyroid atria. As a result, the ISO effects on contractility and relaxation also became higher in hypothyroid atria. Hypothyroidism is associated with decreased activity of cAMP-phosphodiesterase [19]. A lower rate of cAMP breakdown may favor cAMP accumulation in close proximity to SR and thereby also promote the phosphorylation of phospholamban, and hence contractility by ISO in hypothyroid atria.
Comparison of the present results with earlier observations [6]points to important differences between atria and ventricles. Table 1 and Fig. 5 show that hyperthyroid atria exhibited 9 times higher values of +dT/dt, and 14-fold lower phospholamban/SR Ca2+-pump ratios than hypothyroid atria. These thyroid-state-dependent changes are 3–4 times larger than those observed in rat ventricles [6]. According to Fig. 3, hyperthyroid atria possess 2.4 times more SR Ca2+-pump protein than hypothyroid atria. An equivalent difference in that protein has been found between hypothyroid and hyperthyroid ventricles [6]. However, phospholamban decreased 6.7 times in atria (Fig. 3), but only 1.8 times in ventricles [6]under the shift from hypothyroidism to hyperthyroidism. Thus, atrial phospholamban is downregulated more than its ventricular counterpart by thyroid hormones, which explains the large differences observed between changes in the phospholamban/SR Ca2+-pump ratio in these two types of myocardium.
Possibly, these differences are essential for cardiac adaptation to the hyperthyroid state (thyrotoxicosis) characterized by volume overload, myocardial hypertrophy, and tachycardia [1–3]. In these conditions, almost total downregulation of phospholamban results in near-maximal activation of the SR Ca2+-pump in atria, which by increasing atrial contractility ensures efficient ventricular filling despite a shortened duration of diastole.
In conclusion, our results indicate that thyroid hormones increase the contractility, but decrease the inotropic effect of ISO by suppressing the phospholamban/SR Ca2+-pump ratio in rat atria.
Time for primary review 22 days.
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Acknowledgements |
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This work was supported in part by grants from the Estonian Science Foundation and from the German Research Foundation (to R. Vetter, Ve 13611-3).
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References |
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TopAbstract1 Introduction2 Methods3 Results4 DiscussionReferences |
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- Gay R.G., Raya T.E., Lancaster L.D., Lee R.W., Morkin E., Goldman S. Effects of thyroid state on venous compliance and left ventricular performance in rats. Am J Physiol (1988) 254:H81–H88.[Web of Science][Medline]
- Klein I. Thyroid hormone and the cardiovascular system. Am J Med (1990) 88:631–637.[CrossRef][Web of Science][Medline]
- Seppet E.K., Kolar F., Dixon I.M., Hata T., Dhalla N.S. Regulation of cardiac sarcolemmal Ca2+ channels and Ca2+ transporters by thyroid hormone. Mol Cell Biochem (1993) 129:145–159.[CrossRef][Web of Science][Medline]
- Dillmann W.H. Biochemical basis of thyroid hormone action in the heart. Am J Med (1990) 88:626–630.[CrossRef][Web of Science][Medline]
- Beekman R.E., van Hardeveld C., Simonides S. On the mechanism of the reduction by thyroid hormone of β-adrenergic relaxation rate stimulation in rat heart. Biochem J (1989) 259:229–236.[Web of Science][Medline]
- Kiss E., Jakab G., Kranias E.G., Edes I. Thyroid hormone-induced alterations in phospholamban protein expression. Regulatory effects of sarcoplasmic reticulum Ca2+ transport and myocardial relaxation. Circ Res (1994) 75:245–251.
[Abstract/Free Full Text] - Katz AM. Physiology of the heart, 2nd ed. New York: Raven Press, 1992.
- Banerjee S.K. Comparative studies of atrial and ventricular myosin from normal, thyrotoxic, and thyroidectomized rabbits. Circ Res (1983) 52:131–136.
[Abstract/Free Full Text] - Samuel J.-L., Rappaport L., Syrovy I., et al. Differential effect of thyroxine on atrial and ventricular myosin in rats. Am J Physiol (1986) 250:H333–H341.[Web of Science][Medline]
- Bottinelli R., Canepari M., Cappelli V., Reggiani C. Maximum speed of shortening and ATPase activity in atrial and ventricular myocardia of hyperthyroid rats. Am J Physiol (1995) 269:C785–C790.[Web of Science][Medline]
- Laemmli U.K. Cleavage of structural proteins during the assembly of the head bacteriophage. Nature (1970) 227:680–685.[CrossRef][Medline]
- Vetter R., Rupp H. CPT-1 inhibition by etomoxir has a chamber-related action on cardiac sarcoplasmic reticulum and isomyosins. Am J Physiol (1994) 267:H2091–H2099.[Web of Science][Medline]
- Lowry O.H., Rosebrough N.J., Farr A.L., Randall R.J. Protein measurement with the Folin phenol reagent. J Biol Chem (1951) 193:265–275.
[Free Full Text] - Solaro R.J., Briggs F.N. Estimating the functional capabilities of sarcoplasmic reticulum in cardiac muscle. Circ Res (1974) 34:531–540.
[Abstract/Free Full Text] - Barany M. ATPase activity of myosin correlated with speed of muscle shortening. J Gen Physiol (1967) 50(suppl):197–216.
[Abstract/Free Full Text] - Handberg G.M., Ishac E.J.N., Pennefather J.N. Influence of altered thyroid state on the interval–strength relationship of paced left atria of rats. J Cardiovasc Pharmacol (1984) 6:936–942.[Web of Science][Medline]
- Hawthorn M.H., Gengo P., Wei X.-Y., et al. Effect of thyroid status on β-adrenoceptors and calcium channels in rat cardiac and vascular tissue. Naunyn-Schmiedeberg's Arch Pharmacol (1988) 337:539–544.[Web of Science][Medline]
- Kaasik A., Seppet E.K., Ohisalo J.J. Enhanced negative inotropic effect of an adenosine A1-receptor agonist in rat left atria in hypothyroidism. J Mol Cell Cardiol (1994) 26:509–517.[CrossRef][Web of Science][Medline]
- Kaasik A., Elomaa V.-V., Seppet E.K., Ohisalo J.J. Low particulate type IV phosphodiesterase activity in hypothyroid rat atria. J Mol Cell Cardiol (1994) 26:1587–1592.[CrossRef][Web of Science][Medline]
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