atrial-natriuretic-factor and Hypothyroidism

Topics: Animals; Atrial Natriuretic Factor; Blood Volume; Cardiomegaly; Catecholamines; Humans; Hypertension; Hyperthyroidism; Hypothyroidism; Myocardial Contraction; Receptors, Thyroid Hormone; Renin-Angiotensin System; Thyroxine; Triiodothyronine; Vascular Resistance; Vasopressins

Topics: Acute Kidney Injury; Animals; Arrhythmias, Cardiac; Ascites; Atrial Natriuretic Factor; Cardiovascular Diseases; Cerebrovascular Disorders; Heart Failure; Humans; Hypertension; Hyperthyroidism; Hypothyroidism; Kidney; Liver Cirrhosis; Myocardial Infarction; Sodium; Thyroxine

Topics: Atrial Natriuretic Factor; Biomarkers; Humans; Hyperaldosteronism; Hypothyroidism; Inappropriate ADH Syndrome; Vasopressins; Water-Electrolyte Balance

Topics: Adrenal Glands; Aldosterone; Atrial Natriuretic Factor; Heart Failure; Humans; Hyperplasia; Hypothyroidism; Renin-Angiotensin System; Sodium

Thyroid dysfunction is associated with several abnormalities in intermediary metabolism, including impairment of lipolytic response to catecholamines in subcutaneous abdominal adipose tissue (SCAAT). Atrial natriuretic peptide (ANP) is a powerful lipolytic peptide; however, the role of ANP-mediated lipolysis in thyroid disease has not been elucidated. The aim of this study was to investigate the role of thyroid hormones in the regulation of ANP-induced lipolysis as well as in the gene expression of hormone-sensitive lipase, phosphodiesterase 3B (PDE3B), uncoupling protein-2 (UCP2), natriuretic peptide receptor type A, and beta(2)-adrenergic receptor in SCAAT of hyperthyroid and hypothyroid patients. Gene expression in SCAAT was studied in 13 hypothyroid and 11 hyperthyroid age-matched women before and 2-4 mo after the normalization of their thyroid status. A microdialysis study was performed on a subset of nine hyperthyroid and 10 hypothyroid subjects. ANP- and isoprenaline-induced lipolyses were higher in hyperthyroid subjects, with no differences between the groups following treatment. Hormone-sensitive lipase gene expression was higher in hyperthyroid compared with hypothyroid subjects before treatment, whereas no difference was observed following treatment. No differences in gene expression of other genes were observed between the two groups. Following treatment, the gene expression of UCP2 decreased in hyperthyroid, whereas the expression of PDE3B decreased in hypothyroid subjects. We conclude that thyroid hormones regulate ANP- and isoprenaline-mediated lipolysis in human SCAAT in vivo. Increased lipolytic subcutaneous adipose tissue response in hyperthyroid patients may involve postreceptor signaling mechanisms.

Topics: Adult; Aged; Atrial Natriuretic Factor; Body Weight; Catecholamines; Energy Metabolism; Female; Gene Expression Regulation; Humans; Hyperthyroidism; Hypothyroidism; Isoproterenol; Lipolysis; Middle Aged; Regional Blood Flow; Subcutaneous Fat, Abdominal

Natriuretic peptides are produced predominantly in the heart and secreted in response to volume expansion and pressure overload. A wide spectrum of cardiac changes is observed in thyroid dysfunctions. This study investigates mid regional pro A-type (proANP) and N-terminal pro-B-type natriuretic peptide (NTproBNP) levels in different thyroid states and evaluates the effect of L-thyroxine treatment on natriuretic peptides in patients with subclinical hypothyroidism.. Case-control and double-blind, placebo-controlled trial. Sera from 161 female patients (35 with overt, 63 with subclinical hypothyroidism; 10 with overt, 14 with subclinical hyperthyroidism; 40 euthyroid controls) were analysed. ProANP and NT-proBNP were measured at baseline and 48 weeks after L-thyroxine treatment in subclinical hypothyroidism.. Circulating proANP and NT-proBNP levels were higher in hyperthyroid patients than in hypothyroid and euthyroid patients (p <0.001). Plasma proANP levels tended to be lower in overt hypothyroidism than in subclinical hypothyroidism. ProANP and NT-proBNP levels correlated weakly to thyroid stimulating hormone (TSH) (r = -0.3 and -0.2, respectively). The natriuretic peptide levels of subclinical and overt hypothyroid subjects showed no difference with those of euthyroid subjects. L-thyroxine treatment had no effect on natriuretic peptide levels in subclinical hypothyroidism.. Natriuretic peptide levels are altered in different thyroid states with a more pronounced effect in hyperthyroidism than in hypothyroidism. Hyperthyroidism should be considered in patients presenting with unclear symptoms and mildly elevated natriuretic peptide levels, as overt hyperthyroidism results in increased serum A- and B-type natriurectic peptide levels, typically seen in mild heart failure.

Topics: Atrial Natriuretic Factor; Case-Control Studies; Double-Blind Method; Female; Humans; Hyperthyroidism; Hypothyroidism; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Thyroid Function Tests

Decreased plasma concentrations of atrial natriuretic factor (ANF) and of its N-terminal prohormones have been demonstrated in severely hypothyroid patients compared with control subjects, and shown to normalize with thyroxine (T4) replacement therapy. Whether this depends on thyroid hormone deficiency exclusively or is secondary to hemodynamic changes that result from it remains a matter of debate. In a recent investigation dose-related increases in both ANF and N-terminal prohormones of ANF by T4 replacement therapy in incremental doses increased at 4-week intervals were demonstrated. It was suggested that thyroid hormones may enhance synthesis rather than release of atrial peptide hormones. The aim of the present study was to confirm this assumption in hypothyroid patients with normal cardiac performance. Serum N-terminal amino acids 1-98 (ie, pro-ANF 1-98) of pro-ANF was determined in 11 severely hypothyroid patients without pericardial effusion and with normal cardiac left ventricular function. Mean pro-ANF 1-98 concentration before T4 replacement therapy remained unchanged after 10 days on T4 (p = .12). After 2 months of therapy, mean pro-ANF 1-98 was significantly increased compared with pretreatment values (p < .003). A significant correlation to the increase in free T4 (r = 0.48, p < .01) but not to the decrease in thyrotropin (TSH) (r = -0.32, p = .09) was found. The present results indicate that thyroid hormones directly increase pro-ANF 1-98 independently of cardiac hemodynamics in the hypothyroid state.

Topics: Adult; Aged; Atrial Natriuretic Factor; Echocardiography, Doppler; Female; Heart; Humans; Hypothyroidism; Male; Middle Aged; Prolactin; Thyrotropin; Thyroxine; Triiodothyronine

We aimed to investigate the effects of thyroid hormone withdrawal on N-terminal prohormone forms of atrial natriuretic peptide (NT-proANP) and brain natriuretic peptide (NT-proBNP) during radioiodine therapy in female patients with differentiated thyroid cancer (DTC).. Serum concentrations of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), NT-proANP and NT-proBNP were measured in 51 female patients with DTC (48.7 ± 4.2 years) at three time-points: day of radioiodine therapy (t1 - under acute hypothyroidism), 5 days after radioiodine (t2 - under acute hypothyroidism) and 3 months after radioiodine (t3 - under TSH suppression). Thirty healthy euthyroid women served as controls (42.8 ± 5.6 years).. At t1/t2/t3, median NT-proANP was 5.2/1.7/487 pmol/L vs. 297.7 pmol/L in control group (p < 0.001), median NT-proBNP was 50.1/36.5/79.5 pmol/L vs. 64.5 pmol/L (p < 0.001) and median NT-proANP/NT-proBNP ratios was 0.20/0.18/4.81 vs. 4.14 (p < 0.001). In acute hypothyroidism, FT3 levels were positively correlated with NT-proANP (r = 0.38, p = 0.005), NT-proANP/NT-proBNP ratios (r = 0.47, p = 0.001), heart rate (r = 0.39, p = 0.005), and negatively with mean arterial blood pressure (r = -0.58, p < 0.001).. Our results indicate that NT-proANP reflects more accurately direct thyroid hormone effects than NT-proBNP. Thyroid hormone-dependent hemodynamic effects seem to be overlapped on the direct stimulatory effect of thyroid hormones on NT-proANP secretion by cardiac myocytes.

Topics: Adult; Aged; Atrial Natriuretic Factor; Case-Control Studies; Drug Administration Schedule; Female; Humans; Hypothyroidism; Iodine Radioisotopes; Middle Aged; Natriuretic Peptide, Brain; Protein Precursors; Thyroid Gland; Thyroid Neoplasms; Thyrotropin; Triiodothyronine

Topics: Animals; Atrial Natriuretic Factor; Fetal Development; Gene Expression Regulation, Developmental; Hypothyroidism; Male; Myocardium; Rats; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Renin-Angiotensin System

This study assessed the behaviour of angiotensin II (Ang II) receptors in an experimental hypothyroidism model in male Wistar rats. Animals were subjected to thyroidectomy and resting for 14 days. The alteration of cardiac mass was evaluated by total heart weight (HW), right ventricle weight (RVW), left ventricle weight (LVW), ratio of HW, RVW and LVW to body weight (BW) and atrial natriuretic factor (ANF) expression. Cardiac and plasma Ang II levels and serum T3 and T4 were determined. The mRNA and protein levels of Ang II receptors were investigated by RT-PCR and Western blotting, respectively. Functional analyses were performed using binding assays. T3 and T4 levels and the haemodynamic parameters confirmed the hypothyroid state. HW/BW, RVW/BW and LVW/BW ratios and the ANF expression were lower than those of control animals. No change was observed in cardiac or plasma Ang II levels. Both AT1/AT2 mRNA and protein levels were increased in the heart of hypothyroid animals due to a significant increase of these receptors in the RV. Experiments performed in cardiomyocytes showed a direct effect promoted by low thyroid hormone levels upon AT1 and AT2 receptors, discarding possible influence of haemodynamic parameters. Functional assays showed that both receptors are able to bind Ang II. Herein, we have identified, for the first time, a close and direct relation of elevated Ang II receptor levels in hypothyroidism. Whether the increase in these receptors in hypothyroidism is an alternative mechanism to compensate the atrophic state of heart or whether it may represent a potential means to the progression of heart failure remains unknown.

Topics: Angiotensin II; Animals; Atrial Natriuretic Factor; Blood Pressure; Cells, Cultured; Gene Expression Regulation; Hypothyroidism; Male; Myocardium; Myocytes, Cardiac; Random Allocation; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; RNA, Messenger; Thyroid Hormones; Thyroidectomy

High atrial natriuretic peptide (ANP) serum levels are seen in acute renal failure (ARF) due to impaired ANP clearance, but the response of ANP to blood volume expansion is blunted. ARF-associated hypothyroidism influences ANP clearance but it may also play a role in the synthesis and release of ANP because in primary hypothyroidism both mechanisms are disturbed. The aim of this study is to analyze whether thyroxin (T4) supplementation improves the synthesis and release of ANP in ARF.. Four groups of rats were studied: group C (control); group ARF; Group ARF-T4 (ARF supplemented with T4), and group Tx (thyroidectomized). Serum creatinine (SCr), creatinine clearance (CrCl), total T4, total triiodothyronin (T3), plasma ANP, ANP response to acute saline load and atrial content of mRNA-ANP were measured 5 days after ARF induction with potassium dichromate.. CrCl was 1.8 +/- 0.4 ml/min in group C, and it significantly dropped to 0.6 +/- 0.5 in ARF (p < 0.01), T4 improved it (1.7 +/- 0.7 in ARF-T4, p < 0.01) and Tx did not change it. Plasma ANP was higher in ARF as compared with C (152 +/- 23 vs. 52 +/- 21 fmol/l, p < 0.01). In ARF-T4, ANP was higher than in C but lower than in ARF (85 +/- 28 fmol/l, p < 0.01). No changes were observed in Tx rats (48 +/- 17 fmol/l). The atrial content of mRNA-ANP was 0.06 +/- 0.025 mRNA-ANP/mRNA-beta-actin ratio units in group C, it was higher in ARF (0.13 +/- 0.025, p < 0.01) and lower in Tx (0.04 +/- 0.01, p < 0.05) as compared to C. Supplementation with T4 increased the mRNA-ANF content (0.18 +/- 0.2 mRNA-ANP/mRNA-beta-actin ratio units, p < 0.05) over ARF. Plasma ANP response to saline load was 45 +/- 7% in C, but it was reduced in ARF and Tx (20 +/- 10 and 26 +/- 10%, p < 0.01). In ARF-T4 the response was restored (36 +/- 9%, p < 0.01 vs. ARF).. Thyroid hormones modulate the synthesis and release of ANP in ARF. Although the effect is probably direct, T4-induced amelioration of renal damage may also play a significant role by improving the uremic milieu.

Topics: Acute Kidney Injury; Animals; Atrial Natriuretic Factor; Creatinine; Disease Models, Animal; Disease Progression; Heart Atria; Hypothyroidism; Male; Potassium Dichromate; Rats; Rats, Sprague-Dawley; RNA, Messenger; Thyroid Hormones; Thyroxine

It is known that serum angiotensin-converting enzyme (ACE), and plasma atrial natriuretic peptide (p-ANP) levels increase in hyperthyroidism. However, the precise mechanism of the effects of thyroid hormone on ANP release remains to be clarified. No study investigating serum ACE together with p-ANP levels has been performed in experimental hyperthyroid and hypothyroid rabbits. The present study was designed in order to provide additional evidence of increased ANP production and secretion in hyperthyroidism and to investigate the relationships between ANP, ACE and thyroid hormones.. Male New Zealand white rabbits (2.3-3.4 kg) were used throughout the study. Hyperthyroidism was induced by daily intraperitoneal administration of L-thyroxin (50 micrograms/100 g). Hypothyroidism was induced by daily intraperitoneal injection of propylthiouracil (2 mg/100 g body weight). Twelve days after the end of treatment, animals were sacrificed under anesthesia and blood samples were obtained from the aorta for serum ACE and thyroid hormone and p-ANP determinations.. Serum ACE, plasma renin activity (PRA) and p-ANP were higher in hyperthyroid rabbits and lower in hypothyroid rabbits than in euthyroid rabbits. ANP concentration in atria was lower in hyperthyroid rabbits and higher in hypothyroid rabbits than in euthyroid rabbits. p-ANP, PRA and serum ACE levels were positively correlated with serum thyroxin levels. Inverse correlation was found between serum thyroxin and ANP concentration in atria (a-ANP), and between p-ANP and a-ANP.. Our results indicate that not only p-ANP but also serum ACE activity was markedly increased in experimental hyperthyroid rabbits. It was thought that there were both direct and indirect effects of thyroxin on the release of ANP.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Heart Rate; Hyperthyroidism; Hypothyroidism; Male; Peptidyl-Dipeptidase A; Rabbits; Renin; Thyroxine

Topics: Adult; Atrial Natriuretic Factor; Female; Heart Failure; Humans; Hypothyroidism; Male

Hypothyroidism is known to be associated with abnormalities of kidney function; recently, low atrial natriuretic peptide (ANP) plasma levels have been reported. Aim of the study was to asses ANP, sodium and water responsiveness to an acute saline load. Twelve patients with established primary hypothyroidism and 9 control subjects were studied. ANP was determined in plasma by RIA with extraction, prior to and after the infusion of saline, 500 ml/h for 4 hours. On a similar albeit liberal sodium diet hypothyroid patients excreted less sodium and water (74 +/- 33 (SD) mumol/min and 0.69 +/- 0.15 ml/min, respectively) than control subjects (110 +/- 52 mumol/min; P < 0.05 and 1.06 +/- 0.53 ml/min; P < 0.025, respectively). However, the infusion of saline resulted in a 3-fold increase of sodium output and more than 2-fold increase in urine flow. The exaggerated responsiveness in sodium excretion in patients with hypothyroidism was associated with significantly decreased pre-infusion ANP plasma levels (16.1 +/- 11.1 pg/ml vs. 44.4 +/- 14.4 pg/ml; P < 0.001) and also with sluggish response to the volume expansion (+24% vs. +48%). A significant correlation was found between serum T4 levels and plasma ANP concentrations in 8 patients (r = 0.689; P < 0.05). Although hypothyroid patients tend to retain sodium on a liberal salt diet, their kidney is capable of vigorously eliminating excess sodium when challenged with an acute saline load. This exaggerated responsiveness of sodium excretion can be demonstrated in spite of a sluggish response in ANP. Subnormal ANP levels in hypothyroidism are probably the result of thyroid deficiency.

Topics: Adult; Aged; Atrial Natriuretic Factor; Body Water; Case-Control Studies; Female; Humans; Hypothyroidism; Infusions, Intravenous; Kidney; Middle Aged; Radioimmunoassay; Sodium; Sodium Chloride

Long-standing observations that cardiac muscle exists in the walls of the pulmonary and caval veins have recently been confirmed at the molecular level (Lyons et al. [1990] J. Cell Biol. 111:2427-2436; Springall et al. [1988] Thorax 43:44-52; Subramaniam et al. [1991] J. Biol. Chem. 266:24613-24620). Using ventricle- and atrial-specific riboprobes, we determined that the pulmonary myocardium exhibits an atrial pattern of cardiac-specific gene expression. Additionally, the developmental pattern of expression was studied using a riboprobe specific to the alpha-cardiac myosin heavy chain (alpha-MHC) gene transcript. We find that alpha-MHC gene expression is first detectable in the lung between 13.9-14.3 days post-coitum. Extension of the alpha-MHC specific hybridization signal into the pulmonary venous bed progresses through the neonatal period. The data are consistent with the hypothesis that the extension of alpha-MHC gene expression into the lung occurs via the migration of atrial myoblasts into the vein during atrial septation and remodeling of the sinus venosus and pulmonary venous trunk.

Topics: Animals; Animals, Newborn; Atrial Natriuretic Factor; Base Sequence; DNA Probes; Female; Gene Expression; Genes, Switch; Heart Atria; Heart Ventricles; Hypothyroidism; Lung; Male; Mice; Molecular Sequence Data; Myocardium; Myosins; RNA, Messenger; Transcription, Genetic

To assess whether atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) participate in impaired water excretion in patients with hypothyroid states (HS), an oral acute water loading (WL) test (20 ml/kg.BW/45 min) was performed before and after L-thyroxine (T4) treatment in 5 hypothyroid patients. Plasma ANP, AVP, osmolality (Posm), total protein and renal water excretion were simultaneously determined, and these data were compared to the data from five normal subjects (NS). The impaired water excretion rate in HS was entirely improved in the euthyroid states (ES) after T4 therapy for at least 7 months. Plasma ANP in HS was lower than that in NS (5.9 +/- 0.9 vs. 16.5 +/- 3.6 pmol/L, P < 0.05), but increased after T4 treatment (21.2 +/- 5.7 pmol/L, P < 0.05). Plasma AVP in HS (1.6 +/- 0.5 pmol/L) showed a tendency to be lower than those in ES and NS (2.9 +/- 0.4 and 2.9 +/- 0.7 pmol/L), but did not respond to a fall in Posm after WL, unlike ES and NS. Significant positive correlations were noticed between Posm and plasma AVP in ES and NS, but not in HS. These results suggest that not only the impaired release and/or metabolisms of AVP and ANP, but also derangement of renal water and electrolytes handling might induce attenuation of CH2O formation in hypothyroid states.

Topics: Adult; Arginine Vasopressin; Atrial Natriuretic Factor; Diuresis; Female; Humans; Hypothyroidism; Kidney; Male; Middle Aged; Thyroxine; Time Factors; Water

The release of atrial natriuretic peptide (ANP) in vitro in response to the challenge of sodium chloride was investigated in hypothyroid rats. Male rats were injected with propylthiouracil (PTU, 20mg/kg BW, intraperitoneally), or PTU and thyroxine (T4, 20 micrograms/kg BW, subcutaneously) once daily for 14 days before decapitation. Rats injected with saline were used as control. The plasma samples were collected and extracted by Sep-Pak C18 cartridge. The concentrations of ANP in extracted plasma were measured by a radioimmunoassay (RIA). PTU-induced hypothyroidism resulted in decreased concentrations of plasma ANP. Replacement of T4 in PTU-treated hypothyroid rats restored the plasma concentrations of ANP to normal levels. Furthermore, we examined the right atrial ANP contents and the in vitro release of ANP in PTU-treated rats and control animals. The right atrium was excised and divided into 5 equal pieces, one was homogenized with 0.1 N HCl and extracted by Sep-Pak C18 immediately, and the others were incubated with Locke's solution at 37 degrees C. After basal incubation for 30 min, rat atrial tissues were then incubated with 154, 160, or 165 mM NaCl for 30 min. The concentrations of ANP in extracted atrial tissue and medium samples were also measured by RIA. Decreased atrial contents of ANP were noted in hypothyroid rats. The in vitro release of ANP in response to 165 mM sodium ion was significantly lower in PTU than in saline-injected animals. These results suggest that lower concentration of plasma ANP in hypothyroid rats is at least in part due to impairment of stimulation-secretion responses of right atria during thyroid hypofunction in rats.

Topics: Animals; Atrial Natriuretic Factor; Hypothyroidism; In Vitro Techniques; Male; Myocardium; Rats; Rats, Sprague-Dawley; Sodium Chloride

Aim of our study was estimating if TSH could influence the timing of ANP release. About it we observed 70 male subjects: 40 were euthyroid patients aged 42 +/- 5 years (group A); 20 patients treated by thyroxine in doses sufficient for inhibiting TSH release, aged 45 +/- 7 years (group B). A third group (C) was composed by 10 subjects with high basal levels of serum T3 and T4 with no thyrostatic therapy, aged 40 +/- 9 years. These subjects underwent a TRH test estimating at -30', 0', 30', 60', 120' plasma concentrations of TSH, ANP, T3, T4. In reply to physiological stimulus induced on patients of group A we observed a significant increase of TSH values (max at 60') and ANP levels (max at 120'). No significant variations occurred during the TRH test in T3 and T4 concentrations. In groups B and C no important modifications were observed neither in TSH nor in ANP plasma levels. ANP secretion seems to be dependent from the secretory condition of hypothalamus-pituitary-thyroid axis both in physiological and pathological conditions.

Topics: Adult; Atrial Natriuretic Factor; Female; Hemodynamics; Humans; Hyperthyroidism; Hypothalamo-Hypophyseal System; Hypothyroidism; Male; Middle Aged; Models, Biological; Secretory Rate; Thyroid Gland; Thyroid Hormones; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine

This study was designed to examine the involvement of thyroid hormone in the release of brain natriuretic peptide (BNP) from the heart. We measured plasma immunoreactive BNP (ir-BNP) concentrations in patients with untreated hyperthyroidism. We also measured BNP values in experimental rats with hyperthyroidism induced by thyroxine (T4) and in rats with hypothyroidism induced by propylthiouracil (PTU). The in vitro effects of triiodothyronine (T3) and T4 on the release of BNP were examined in newborn rat atrial and ventricular myocytes in primary culture. Plasma BNP levels were increased in hyperthyroid patients compared with normal control subjects. Plasma BNP levels were increased in hyperthyroid rats and decreased in hypothyroid rats compared with euthyroid rats. Plasma BNP level was correlated with serum T4 level in hyperthyroid patients and hyperthyroid rats. A major component of ir-BNP in plasma from hyperthyroid patients was human BNP-32 and that in plasma from hyperthyroid rats was rat BNP-45. T4 and T3 stimulated release of ir-BNP from both cultured atrial and ventricular myocytes in a dose-dependent manner. Plasma BNP concentration is frequently increased in hyperthyroidism, and thyroid hormone may regulate BNP release from both atrial and ventricular myocytes.

Topics: Adult; Animals; Atrial Natriuretic Factor; Brain Chemistry; Cells, Cultured; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Myocardium; Propylthiouracil; Radioimmunoassay; Rats; Rats, Wistar; Thyroxine; Triiodothyronine

Thyroid hormone effects on myocardial gene expression have been well defined in animal models, but their relationship to the pathogenesis of cardiac dysfunction 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 of myocardial 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 alpha-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.

Topics: Actins; Adenosine Triphosphatases; Adult; Atrial Natriuretic Factor; Base Sequence; Calcium-Binding Proteins; Cardiomyopathy, Dilated; DNA; Gene Expression; Heart; Heart Function Tests; Humans; Hypothyroidism; Male; Molecular Sequence Data; Myocardium; Myosins; Oligodeoxyribonucleotides; Polymerase Chain Reaction; Receptors, Adrenergic, beta; RNA; RNA, Messenger; Thyroid Function Tests

Plasma atrial natriuretic hormone (ANH) values were evaluated in 28 hyperthyroid patients and in 11 hypothyroid patients and compared with 20 healthy subjects. In hyperthyroid patients plasma ANH basal levels were significantly (p less than 0.01) higher (14.2 +/- 1.6 pmol/l) than in controls (7.8 +/- 0.4 pmol/l) and in hypothyroid patients (6.4 +/- 0.3 pmol/l). No significant differences were found between controls and hypothyroid patients. The propranolol-induced decrease in heart rate in hyperthyroid patients did not significantly affect the plasma ANH values. Conversely, after the methimazole-induced euthyroidism a return within the normal range of ANH values was observed. The thyroxine replacement in hypothyroid patients determined a small but significant (p less than 0.05) increase in plasma ANH values. Observed data suggest that in humans thyroid hormones may influence plasma ANH concentrations independently of their effect on heart rate.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Female; Heart Rate; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged; Propranolol; Thyroxine

The effect of altered thyroidal status on levels of immunoreactive (ir)- atrial natriuretic peptide (ANP) in serum and the four cardiac chambers, and of tissue ANP mRNA, was determined in groups of rats given vehicle, thyroxine (T4), propylthiouracil (PTU) or T4 plus PTU for 3 weeks. Serum levels of ir-ANP were approximately 3-fold higher in T4-treated animals compared with control; levels in PTU or PTU/T4 groups were not different from control. Right ventricular ANP mRNA was below detection; in other chamber, levels rose with T4, alone or plus PTU, and fell after PTU compared with control. Atrial ir-ANP levels were unchanged by T4, but increased (left atrium, LA) or decreased (right atrium, RA) after PTU alone. After PTU/T4, some indices (e.g. tissue weight) remained at control levels, others (e.g. ANP mRNA levels) were equivalent to levels in the T4-alone group, and others (e.g. LA ir-ANP) were equivalent to those seen with PTU alone. We conclude that the role of thyroid hormones on ANP synthesis may be similar between chambers but their effects on release appear to differ widely. The extent to which this represents secondary rather than direct effects, or possible T3-versus T4-specific events, awaits elucidation.

Topics: Animals; Atrial Natriuretic Factor; Heart Ventricles; Hyperthyroidism; Hypothyroidism; Male; Myocardium; Nucleic Acid Hybridization; Propylthiouracil; Rats; Rats, Inbred Strains; RNA, Messenger; Thyroid Hormones; Thyroxine; Triiodothyronine

In order to assess a possible involvement of thyroid hormone in atrial natriuretic peptide (ANP), experimentally induced hyper- and hypothyroid rats were employed, and the immunoreactive rat ANP (IR-ANP) concentrations in plasma, atria and brain regions including the hypothalamus were measured by a specific radioimmunoassay. Plasma IR-ANP concentration in hypothyroid rats was 14.5 +/- 2.9 (mean +/- SD) fmol/ml, significantly lower than that in control rats (p less than 0.05 vs control of 24.9 +/- 9.7 fmol/ml). Plasma IR-ANP concentration in hyperthyroid rats was 66.4 +/- 9.7 fmol/min, significantly higher than that in the controls (p less than 0.01). Atrial IR-ANP concentration in hyperthyroid rats was significantly lower than that in the controls (79.9 +/- 11.1 nmol/g vs 133.5 +/- 21.2 nmol/g (control), p less than 0.05), though no significant change was observed in atrial IR-ANP concentration in hypothyroid rats. While hypothalamic ANP concentration in hypothyroid rats was significantly lower than that in the controls (17.5 +/- 3.5 pmol/g vs 31.9 +/- 1.9 pmol/g (control), p less than 0.05), there was no significant change of that in the hyperthyroid rats. On reverse phase high performance liquid chromatography, the major peak in plasma and hypothalamus extract was thought to be identical to synthetic alpha-rat ANP (1-28). These results may suggest that in the hyperthyroid state an excessive amount of ANP is released from atria into the blood, and that in the central nervous system thyroid hormone involve ANP metabolism being different from the atrium.

Topics: Animals; Atrial Natriuretic Factor; Chromatography, High Pressure Liquid; Heart Atria; Hyperthyroidism; Hypothalamus; Hypothyroidism; Radioimmunoassay; Rats; Rats, Inbred Strains

A group of patients with primary hypothyroidism has been studied, and it is reported that low serum levels of thyroid hormones are accompanied by low plasma atrial natriuretic peptide (ANP) concentrations. While the correlation between ANP and thyroid hormone levels is strong, no correlation was found between ANP and heart rate or arterial blood pressure. It is suggested that thyroid hormones directly stimulate the release of ANP from atrial cardiocytes.

Topics: Adult; Atrial Natriuretic Factor; Female; Humans; Hypothyroidism; Male; Middle Aged; Thyrotropin; Thyroxine; Triiodothyronine

The effect of thyroid hormone on circulating levels of atrial natriuretic peptide (ANP) was studied in experimental hyperthyroid and hypothyroid rats. Plasma ANP was 102 +/- 5 pg/ml in euthyroid rats, 82 +/- 4 pg/ml in hypothyroid rats, and 138 +/- 11 pg/ml in hyperthyroid rats. We have also measured immunoreactive ANP in the atria of euthyroid, hypothyroid, and hyperthyroid rats. ANP content and concentration in the atria were lower (546 +/- 32 pg/mg tissue) in hyperthyroid rats than in hypothyroid rats (802 +/- 74 pg/mg tissue). Right atrium from euthyroid, hypothyroid, and hyperthyroid rats was superfused with a modified Langendorff preparation. Spontaneous release of ANP was significantly higher from the hyperthyroid rats (20 +/- 2 pg.min-1.mg-1) than from the hypothyroid rats (5.6 +/- 0.5 pg.min-1.mg-1). ANP release from the euthyroid rats was 9.3 +/- 1.2 pg.min-1.mg-1. These results indicate hyperthyroidism causes an increase in ANP secretion and a decreased release occurs during hypothyroidism.

Topics: Animals; Atrial Natriuretic Factor; Heart Atria; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Male; Methimazole; Myocardium; Rats; Rats, Inbred Strains; Thyroxine

Hyperthyroidism characteristically has natriuresis and vasodilation associated with it, whereas hypothyroidism is associated with impaired water excretion and vasoconstriction. This investigation was designed to determine if the plasma concentration(s) of three newly described hormones synthesized in the heart are increased in patients with hyperthyroidism and/or decreased in patients with hypothyroidism compared to normal subjects. The three hormones consist of amino acids 1-30, 31-67, and 99-126 (ANF) of the 126 amino acid prohormone of atrial natriuretic factor. Prohormone atrial natriuretic peptides (pro ANFs) 1-30, 31-67, and ANF were increased threefold, fourfold, and twofold respectively in hyperthyroid patients compared to the mean circulating concentration of 54 healthy persons without thyroid disease. Plasma concentrations of the three peptides in hypothyroid patients were only one-half that of the 54 persons without thyroid disease. With appropriate treatment of hyperthyroidism and hypothyroidism, the levels of the three peptides returned to normal. The peptide hormones increased proportionately with the increasing dosages of L-thyroxine of 50 micrograms/day and 100 micrograms/day in the hypothyroid patients. In persons with hypothyroidism complicated by congestive heart failure, the levels of pro ANFs 1-30, 31-67, and 99-126 were increased, demonstrating that abnormalities of salt and water metabolism are a strong stimulus to the release of these peptides.

Topics: Adult; Atrial Natriuretic Factor; Female; Heart Failure; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Osmolar Concentration; Peptide Fragments; Protein Precursors; Reference Values; Thyroid Hormones

Topics: Adult; Aged; Atrial Natriuretic Factor; Homeostasis; Humans; Hypothyroidism; Middle Aged; Thyroxine

The effect of thyroid hormone on atrial natriuretic factor (ANF) production was investigated in hypothyroid, euthyroid, and hyperthyroid rats by measuring levels of ANF mRNA and ANF in myocardium. ANF mRNA was quantitated by dot blot hybridization, and ANF by specific RIA. Relative ANF mRNA concentrations (ANF mRNA to 18S RNA) were determined for right atria, left atria, and ventricular apices. The total chamber content of ANF mRNA was estimated (concentration X total chamber RNA) and used as a measure of each tissue's synthetic capacity. For both atrial tissues, ANF mRNA contents were significantly higher in hyperthyroidism. In right atria, mean ANF mRNA contents in hypothyroidism and hyperthyroidism were 41% and 176%, respectively, of that in euthyroidism (P less than 0.05, by analysis of variance). Left atrial ANF mRNA contents in hypothyroidism and hyperthyroidism were 94% and 272%, respectively, of the euthyroid value (P less than 0.05). In contrast, atrial ANF mRNA concentrations did not differ significantly between thyroid states. In ventricle, ANF mRNA content and concentration were both correlated with serum T4 concentration. Ventricular ANF mRNA contents in hypothyroidism and hyperthyroidism were 31% and 178%, respectively, of that in euthyroidism (P less than 0.02). The concentration of ventricular ANF mRNA was also significantly increased in hyperthyroidism (P less than 0.05). Tissue content of ANF increased in the hyperthyroid right atria and decreased in the hyperthyroid left atria and ventricles. These observations suggest that increased ANF production by both atria and, to a lesser extent, by the ventricles contributes to the higher circulating ANF levels reported in hyperthyroidism. Furthermore, hyperthyroidism is associated with a specific increase in ventricular ANF mRNA expression as has been observed in other conditions causing ventricular hypertrophy.

Topics: Animals; Atrial Natriuretic Factor; Heart Atria; Heart Ventricles; Hyperthyroidism; Hypothyroidism; Male; Myocardium; Propylthiouracil; Rats; Rats, Inbred Strains; Reference Values; RNA, Messenger; Thyroid Gland; Thyroxine; Transcription, Genetic

To address the role of atrial natriuretic factor (ANF) in hypothyroidism in the control of cardiorenal-endocrine function during volume loading, the relationships between atrial pressure, ANF, the renin-angiotensin-aldosterone system, and renal hemodynamic and excretory function were examined during and after acute 10% body wt saline volume infusion in pentobarbital-anesthetized hypothyroid dogs (n = 8). Hormonal changes before and after thyroidectomy were also evaluated. Four to 6 wk after thyroidectomy, ANF decreased and arginine vasopressin (AVP) and plasma renin activity (PRA) increased. Acute saline volume expansion caused an increase in ANF and decreases in AVP and PRA. Atrial pressure increased throughout volume expansion. Despite the absence of an increase in glomerular filtration rate (GFR) during volume expansion, urinary sodium excretion increased due to a marked rise in fractional excretion of sodium. These studies demonstrate that in hypothyroidism 1) ANF is decreased; 2) despite the decrease in basal ANF, increases in atrial pressure can stimulate relase of ANF; 3) despite the absence of an increase in GFR during volume expansion, fractional excretion of sodium increases associated with an increase in ANF; and 4) a lack of an increase in GFR during volume expansion is not related to an inability to increase ANF.

Topics: Aldosterone; Animals; Atrial Natriuretic Factor; Blood Volume; Dogs; Glomerular Filtration Rate; Hypothyroidism; Natriuresis; Renin; Renin-Angiotensin System

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Diuresis; Glomerular Filtration Rate; Hematocrit; Hypothyroidism; Kidney; Kidney Concentrating Ability; Male; Potassium; Rats; Rats, Inbred Strains; Sodium; Thyroidectomy

To examine a possible role of atrial natriuretic peptide (ANP) in water and electrolyte disturbances associated with thyroid disorders, plasma ANP levels were studied in patients with hyper- and hypothyroidism. In 5 of the 21 hyperthyroid patients, including two patients with atrial fibrillation and two patients with mild cardiomegaly, the plasma ANP concentration was increased when compared to normal subjects. After treatment with methimazole or propylthiouracil, the plasma ANP concentration fell to normal in 4 patients, while it remained high in one patient who had persistent atrial fibrillation. No significant correlation was found between plasma ANP and the heart rate in untreated hyperthyroid patients. Plasma ANP was within the normal range in all 8 patients with hypothyroidism. During treatment with T4, the plasma ANP concentration increased in 6 of the 7 patients. Chest X-ray films and ultrasonic echocardiography demonstrated pericardial effusion in 4 of these patients before therapy. A weak but significant correlation was found between the plasma ANP and T4 concentration, and between plasma ANP and free T4 in hyper- and hypothyroid patients before and after treatment. These results indicate that abnormalities in ANP dynamics in thyroid disorders may probably be caused by hemodynamic changes resulting from a thyroid hormone excess or deficiency.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Female; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Thyroid Gland; Thyroxine

In order to assess the possible involvement of thyroid hormone in alpha human atrial natriuretic peptide (alpha hANP), we investigated the plasma and urine ANP concentration in patients with primary hyperthyroidism and hypothyroidism. Plasma and urine were extracted through Sep-Pak C18 cartridges and the urine ANP concentration was corrected by urine creatinine (cre. mg/dl) and expressed as fmol/mg.cre.. The plasma ANP concentration in patients with untreated hyperthyroidism (32.3 +/- 7.0 fmol/ml; n = 22) was higher than in normal subjects (p less than 0.01 vs control; 6.2 +/- 0.7 fmol/ml). After restoration to euthyroidism, the plasma ANP concentration (patients with treated hyperthyroidism) fell to normal (8.9 +/- 1.9 fmol/ml). The plasma ANP concentration in patients with untreated hypothyroidism (14.1 +/- 3.0 fmol/ml; n = 7) was higher than normal, but in two of them there was mild renal dysfunction and an incomplete right blundle branch block in the electrocardiogram. It was possible that these factors contributed to the observed increase in plasma ANP. However, a significant positive correlation was found between plasma ANP and free thyroxine (n = 40, r = 0.449; p less than 0.01) and free triiodothyronine (n = 40, r = 0.546; p less than 0.01). The urine ANP concentration in patients with untreated hyperthyroidism was markedly higher than in normal subjects (p less than 0.01), but in untreated hypothyroidism not significantly different from normal.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Child; Chromatography, High Pressure Liquid; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Radioimmunoassay; Thyroid Hormones

Topics: Atrial Natriuretic Factor; Female; Homeostasis; Humans; Hypertension; Hypothyroidism; Pre-Eclampsia; Pregnancy

The effect of hypothyroidism on circulating levels of atrial natriuretic peptide (ANP) was studied in 11 hypothyroid patients (aged 11-65 yr; mean, 31 yr) and 13 normal subjects (aged 28-39 yr; mean, 32 yr). Plasma ANP was 32 +/- 9 (+/- SD) pg/ml in normal subjects and 20 +/- 5 pg/ml in the hypothyroid patients (P less than 0.005). In 7 hypothyroid patients, plasma ANP levels were measured after 10-14 weeks of L-T4 therapy. ANP increased from 22 +/- 5 to 46 +/- 18 pg/ml (P less than 0.02), along with an increase in mean serum T4 from 0.6 +/- 0.5 to 8.1 +/- 2.5 micrograms/dl (P less than 0.001). Thus, hypothyroidism is characterized by decreased circulating levels of ANP which are reversed by L-T4 therapy.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Child; Female; Humans; Hypothyroidism; Male; Middle Aged; Thyrotropin; Thyroxine

Plasma concentrations of atrial natriuretic peptides were measured in 32 normal control subjects, 25 patients with hyperthyroidism, and 18 patients with hypothyroidism. Atrial natriuretic peptide values were measured before and after successful therapy with methimazole or 1-thyroxine. Plasma atrial natriuretic peptide concentration was increased in patients with hyperthyroidism (48.0 +/- 19.5 pg/ml) but was decreased in patients with severe hypothyroidism (16.3 +/- 5.7 pg/ml) compared with values in normal control subjects (31.2 +/- 9.5 pg/ml). There was no significant difference between values in normal control subjects and mildly hypothyroid patients (35.0 +/- 12.2 pg/ml). The plasma atrial natriuretic peptide concentration was correlated with the serum thyroxine level and heart rate. The elevated atrial natriuretic peptide concentration in hyperthyroidism decreased, whereas the reduced atrial natriuretic peptide concentration in severe hypothyroidism increased, compared with the initial value after successful therapy. These results suggest that plasma atrial natriuretic peptide concentration is frequently increased in hyperthyroidism and is frequently decreased in severe hypothyroidism, and that thyroid hormone is one of the regulatory factors for circulating atrial natriuretic peptides.

Topics: Adult; Atrial Natriuretic Factor; Female; Heart Rate; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Reference Values; Thyroxine

Atriopeptin (AP) is a polypeptide produced by atrial myocytes that is capable of inducing diuresis, natriuresis, and vasodilatation. Because thyroid dysfunction is known to be associated with alterations in both renal function and vasomotor control, we investigate the possible effects of varying thyroid function on AP in humans and rats. Plasma AP concentrations were determined in hyperthyroid and hypothyroid patients and normal subjects. Plasma AP was also measured in some patients after the iv infusion of 1 L 150 mmol/L NaCl and after treatment of hyperthyroidism or hypothyroidism. Plasma and atrial AP concentrations were measured in hyperthyroid, euthyroid, and hypothyroid rats. Plasma AP concentrations did not differ in the hyperthyroid (n = 22), euthyroid (n = 45), and hypothyroid (n = 16) subjects [47.1 +/- 18.2 (mean +/- SD), 45.1 +/- 28.9, and 42.4 +/- 20.0 pg/mL, respectively]. After NaCl infusion, mean plasma AP concentrations did not increase significantly in any of the three groups. Treatment of hyperthyroidism and hypothyroidism did not result in a significant change in plasma AP levels. In contrast, plasma AP concentrations were significantly higher in T4-treated (hyperthyroid) rats than in either euthyroid or propylthiouracil-treated (hypothyroid) rats [621 +/- 17 vs. 266 +/- 41 (P less than 0.01) and 210 +/- 28 pg/mL (P less than 0.001), respectively], whereas atrial AP contents were similar in the three groups of rats. We conclude that hyperthyroidism and hypothyroidism in man are not associated with significantly altered plasma AP concentrations. The higher plasma AP levels in T4-treated rats may reflect the relatively shorter duration or greater severity of thyroid dysfunction or thyroid hormone-induced myocardial hypertrophy in the animals.

Topics: Adult; Animals; Atrial Natriuretic Factor; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Rats; Rats, Inbred Strains; Thyroid Function Tests; Thyroid Gland

Topics: Adrenal Insufficiency; Atrial Natriuretic Factor; Blood Pressure; Cushing Syndrome; Humans; Hyperaldosteronism; Hypertension, Malignant; Hyperthyroidism; Hypothyroidism; Inappropriate ADH Syndrome

To investigate the involvement of thyroid hormone on the release of atrial natriuretic polypeptide (ANP), we have measured immunoreactive ANP in the atria and plasma of experimental hyperthyroid and hypothyroid rats. Plasma ANP was higher (p less than 0.05) in hyperthyroid rats and was lower (p less than 0.05) in hypothyroid rats than in euthyroid rats. ANP content and concentration in the atria were lower (p less than 0.01) in hyperthyroid rats than in hypothyroid rats. An inverse correlation was found between the plasma ANP and ANP concentration in the atria (n = 15, r = 0.60, p less than 0.01). The results indicate an increased systemic release of ANP from the atria in hyperthyroidism and a decreased systemic release in hypothyroidism.

Topics: Animals; Atrial Natriuretic Factor; Body Weight; Heart Atria; Hemodynamics; Hyperthyroidism; Hypothyroidism; Male; Radioimmunoassay; Rats; Rats, Inbred Strains