Modulation of Atrial Natriuretic Factor by Thyroid Hormone: Messenger Ribonucleic Acid and Peptide Levels in Hypothyroid, Euthyroid, and Hyperthyroid Rat Atria and Ventricles*

Ladenson, Paul W.; Bloch, Kenneth D.; Seidman, J. G.

doi:10.1210/endo-123-1-652

Cited by 57 publications

(30 citation statements)

References 37 publications

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“…Furthermore, it is unlikely that thyroid hormone per se was responsible for the observed changes in expression of these genes. In animal models, hypothyroidism has not been associated with significant changes in expression of either the phospholamban (26) or ANF (27) genes, whereas experimental hyperthyroidism actually decreases myocardial phospholamban gene expression and increases myocardial ANF mRNA levels. These previously reported effects are opposite those observed with reversal of this patient's dilated cardiomyopathy.…”

mentioning

confidence: 99%

Reversible alterations in myocardial gene expression in a young man with dilated cardiomyopathy and hypothyroidism.

Ladenson

Sherman

Baughman

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

158

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Thyroid hormone effects on myocardial gene expression have been well defined in animal models, but their relationship to the pathogenesis of cardiac dysmuction in hypothyroid humans has been uncertain. We evaluated a profoundly hypothyroid young man with dilated cardiomyopathy. Before and during 9 months of thyroxine therapy, serial assessment ofmyocardial performance documented substantial improvements in the left ventricular ejection fraction (16-37%), left ventricular end-diastolic diameter (7.8-5.9 cm), and cardiac index (1.4-2.7 liters'min-1-m-2). Steady-state levels of mRNAs encoding selected cardiac proteins were measured in biopsy samples obtained before and after thyroxine replacement. In comparison with myocardium from nonfailing control hearts, this patient's pretreatment a-myosin heavy-chain mRNA level was substantially lower, the atrial natriuretic factor mRNA level was markedly elevated, and the phospholamban mRNA level was decreased. All of these derangements were reversed 9 months after restoration of euthyroidism. These observations in an unusual patient with profound myxedema and cardiac dilatation permit correlation between the reversible changes in myocardial function and steady-state mRNA levels in a cardiomyopathy. They suggest that alterations in gene expression in the dilated myopathic heart may be correctable when a treatable cause is identified.Most patients with dilated cardiomyopathy have a poor long-term prognosis, with progressive myocardial dysfunction. Rarely, a metabolic etiology responsive to specific therapy is identified. For example, previous reports have described reversal of the hemodynamic and morphologic abnormalities of cardiomyopathy with treatment of pheochromocytoma (1), hypocalcemia (2, 3), and carnitine deficiency (4, 5). The "myxedema heart" was first described by Zondek (6), who noted a dilated cardiac silhouette, slow indolent heart action, and low electrocardiographic voltage, which were all corrected by thyroid hormone therapy. Although invasive (7) and noninvasive (8) studies have since confirmed that thyroid hormone deficiency is associated with a reversible decrease in myocardial contractility, it has remained controversial whether hypothyroidism alone can cause a dilated cardiomyopathy and clinical heart failure. Furthermore, although effects of thyroid hormones on myocardial myosin isoenzyme expression (9, 10), 3-adrenergic receptor number (11), sarcoplasmic reticulum calcium exchange (12), and guanine nucleotide-binding regulatory proteins (13) have all been described in experimental animals, the fundamental pathogenesis of myocardial dysfunction caused by thyroid hormone deficiency in humans has remained uncertain.We report a young man with a dilated cardiomyopathy and profound hypothyroidism. During 9 months of thyroid hormone replacement therapy, serial clinical observations and noninvasive cardiovascular function tests documented substantial improvement in myocardial performance. Quantitation of steady-state mRNA levels in endomyocardial biops...

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mentioning

confidence: 99%

Reversible alterations in myocardial gene expression in a young man with dilated cardiomyopathy and hypothyroidism.

Ladenson

Sherman

Baughman

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

158

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“…Right atrial proANP mRNA content in hypothyroidism and hyperthyroidism was 41% and 176%, respectively, of euthyroidism (31). Ventricular proANP mRNA content in hypothyroidism and hyperthyroidism was 31% and 178%, respectively, of that in euthyroidism.…”

Section: Enhancement Of Proanp Gene Expressionmentioning

confidence: 89%

Atrial Natriuretic Peptide Prohormone Gene Expression: Hormones and Diseases That Upregulate its Expression

Vesely

2002

IUBMB Life

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“…In addition to hypertrophy, ANP gene expression in the adult ventricle has also been shown to be induced by exposure to a hormonal stimulus (Gardner et al, 1986;Day et al, 1987;Ladenson et al, 1988;Ruskoaho et al, 1989b). It has been proposed that the reinduction of the ANP gene represents regression of the ventricular myocyte toward its earlier developmental form Zeller et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

Effect of phorbol ester on the release of atrial natriuretic peptide from the hypertrophied rat myocardium

Kinnunen¹,

Taskinen²,

Järvinen³

et al. 1991

British J Pharmacology

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1 To determine the cellular mechanisms of atrial natriuretic peptide (ANP) release from ventricular cardiomyocytes, the secretory and the cardiac effects of a phorbol ester, 12-0-tetradecanoyl-phorbol-13-acetate (TPA), known to stimulate protein kinase C activity in heart cells, were studied in isolated, perfused heart preparations from 2-and 21-month-old Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. TPA was added to the perfusion fluid for 30 min at a concentration of 46 nm after removal of atrial tissue. Additionally, atrial and ventricular levels of immunoreactive ANP (IR-ANP) and ANP mRNA, the distribution of ANP within ventricles as well as the relative contribution of atria and ventricles in the release of ANP were studied. 2 Ventricular hypertrophy that gradually developed in hypertensive rats resulted in remarkable augmentation of ANP gene expression, as reflected by elevated levels of immunoreactive ANP and ANP mRNA. The total amount of IR-ANP in the ventricles of the SHR rats increased 41 fold and ANP mRNA levels 12.9 fold from the age of 2 to 21 months. At the age of 21 months, levels of IR-ANP and ANP mRNA in the ventricles of SHR rats were 5.4 fold and 3.7 fold higher, respectively, than in the normotensive WKY rats. Immunohistochemical studies demonstrated ANP granules within the hypertrophic ventricles of the old SHR rats, but not within normal ventricular tissue. 3 In isolated perfused heart preparations, the severely hypertrophied ventricular tissue of SHR rats after atrialectomy secreted more ANP into the perfusate than did the control hearts. The phorbol ester TPA caused a marked vasoconstriction in both the 2-month and 21-month old normal and hypertrophied hearts. Interestingly, the ANP release from the hypertrophied ventricles of the old SHR rats increased considerably (from 413 + 30 to the maximum of 623 + 75 pgml-1, F = 10.8, P < 0.001, two-way analysis of variance), whereas only a small increase was seen in old WKY rats and no effect was observed in young animals of either strain. When intact rat hearts (without atrialectomy) were used, infusion of phorbol ester also increased the ANP secretion into the perfusate in young animals. 4 Our present results indicate that the phorbol ester TPA increases the release of ANP from the hypertrophied, but not from normal rat myocardium. Thus, hypertrophied rat ventricular myocytes appear to possess the cellular mechanisms necessary to secrete ANP by a regulated pathway. The results further suggest that protein kinase C activity may be involved in the the regulation of ANP secretion from ventricular cells, as has been shown earlier for atrial myocytes.

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Modulation of Atrial Natriuretic Factor by Thyroid Hormone: Messenger Ribonucleic Acid and Peptide Levels in Hypothyroid, Euthyroid, and Hyperthyroid Rat Atria and Ventricles*

Cited by 57 publications

References 37 publications

Reversible alterations in myocardial gene expression in a young man with dilated cardiomyopathy and hypothyroidism.

Reversible alterations in myocardial gene expression in a young man with dilated cardiomyopathy and hypothyroidism.

Atrial Natriuretic Peptide Prohormone Gene Expression: Hormones and Diseases That Upregulate its Expression

Effect of phorbol ester on the release of atrial natriuretic peptide from the hypertrophied rat myocardium

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