atrial-natriuretic-factor and Hyperaldosteronism

Essential hypertension probably results from combinations of small genetic variations that are partly normal variations and may not be appreciably harmful individually. Strategies to identify genes contributing to hypertension are discussed in this review. Gene targeting approaches, especially gene titration, have been used in these studies of hypertension. Gene titration experiments vary the expression of a chosen gene product by generating animals having different numbers of copies of the gene coding for the product. Gene titration is powerful for analyzing quantitative variations seen in common polygenic disorders, such as kidney diseases, diabetes mellitus, and atherosclerosis, as well as hypertension, because it allows tests of causation by determining the effects on a phenotype by changes in expression of the altered gene and because it matches normal quantitative variations more closely than is possible with classic transgenic mice. The use of zero-copy (gene "knockout") animals generated by gene disruption for studies of qualitative gene effects is also discussed. These various gene targeting experiments help identify genes regulating BP, promote a better understanding of the pathophysiology of the condition, and help identify potential targets for therapies.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Endothelin-1; Gene Targeting; Humans; Hyperaldosteronism; Hypertension; Mice; Mice, Knockout; Models, Genetic; Mutation; Nitric Oxide Synthase; Receptor, Bradykinin B2; Receptors, Bradykinin; Renin-Angiotensin System; Syndrome

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

Although it has been recognized for almost 70 years that there is a substantial genetic component to the pathogenesis of hypertension, only recently have systematic efforts been made to identify the responsible genetically determined mechanisms. In the case of several rare syndromes, spectacular progress has been made in identifying the underlying molecular mechanisms responsible for the clinical expression. Glucocorticoid-suppressible aldosteronism and Liddle's syndrome, each inherited as an autosomal-dominant condition, complete the list. In the case of randomly selected patients and families with essential hypertension, inheritance involves many genes and progress has been far more modest. Probably the most promising lead has involved the genes governing the structure of angiotensinogen, the substrate in the renin reaction. Linkage has been established and confirmed. At the moment, however, neither the relation of the genetic abnormality to the underlying mechanisms, nor the contribution of this abnormality to hypertension in the individual patient, has been defined. We know less about other candidate genes, with the exception of studies that rigorously ruled out a contribution. The development of the concept of the "intermediate phenotype," a physiological feature that makes it possible to identify a homogeneous subpopulation, should help to sort out many of these issues. Unfortunately, the identification and characterization of intermediate phenotypes is substantially more difficult at the moment than are the genetic studies, and so progress is likely to be slow. The field is complicated by the reporting of claims made on the basis of small patient samples. In the case of polymorphisms in the angiotensin-converting enzyme gene as a risk factor for tissue injury, for example, substantial follow-up studies have systematically failed to confirm the original report, which was based on a small patient sample. The fact that the same DNA collection is likely to be examined many times for multiple gene candidates creates a setting in which type I errors are likely, and so we are likely to see many more examples. Caveat lector. Again, the development of relevant intermediate phenotypes will make the spurious association less likely.

Topics: Angiotensinogen; Atrial Natriuretic Factor; Genes, Dominant; Humans; Hyperaldosteronism; Hypertension; Nitric Oxide Synthase; Peptidyl-Dipeptidase A; Phenotype; Polymorphism, Genetic; Racial Groups; Renin-Angiotensin System; Syndrome

The diagnosis of primary aldosteronism (PA) is based on the finding of the combination of elevated urinary and/or plasma aldosterone and suppressed renin activity in patients with hypertension and hypokalemia. However, PA consists in a number of subsets, and diagnostic criteria for a correct identification of surgically remediable forms are of great interest. The methods and the results concerning our series of 113 patients with primary aldosteronism are presented in this review. Aldosterone producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) were the most frequent forms, 51% and 44% respectively. They had similar BP levels, but hypokalemia was most frequently found in APA. Urinary and upright plasma aldosterone were similar, but supine plasma aldosterone was lower in IHA. Plasma aldosterone response to upright posture and angiotensin II infusion was absent in most cases of APA and present in IHA, but occasionally renin-responsive adenoma were found. Captopril failed to decrease plasma aldosterone in most patients with APA, and in a subgroup of patients with IHA. Patients with adenoma had also higher values of the aldosterone precursor 18-OH-B, and of atrial natriuretic peptide (ANP), probably as a consequence of a greater degree of volume expansion. Among morphological studies, CT scan and adrenal radio-cholesterol scintiscan provided similar results (85% accuracy): adrenal vein catheterization clarified almost all the remaining cases. Among the subsets of PA, 3 familiar cases of dex-suppressible hyperaldosteronism were recognized, with characteristically high levels of aldo, 18-OH-B, 18-OH-cortisol and 18-oxo-cortisol, due to the genetic abnormalities of the 11-18 hydroxylase system.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenoma; Adrenal Cortex; Adrenal Cortex Neoplasms; Atrial Natriuretic Factor; Captopril; Carcinoma; Cytochrome P-450 CYP11B2; Cytochrome P-450 Enzyme System; Dexamethasone; Diagnostic Imaging; Humans; Hyperaldosteronism; Hyperplasia; Posture; Renin; Retrospective Studies; Steroid 11-beta-Hydroxylase

Atrial natriuretic peptide is a recently discovered cardiac hormone with natriuretic, vasodilatory and hypotensive activities. The role of this hormone in the pathophysiology of hypertension is of particular interest. In contrast to an earlier concept, a deficiency of the atrial peptide could not be found in animal models of hypertension or in patients. ANP plasma levels were elevated in SHR with accelerated hypertension, in salt-sensitive Dahl rats, in rats with DOCA-salt-hypertension and in animals with renovascular hypertension. Elevated ANP levels under these conditions can be explained by an expansion of the intravascular volume or by an elevated atrial wall stretch induced by the hypertension itself. In patients with primary hypertension, plasma levels of the peptide are raised in some patients and are normal in others. Plasma ANP levels correlate with age, blood pressure and signs of left ventricular hypertrophy. A negative correlation is described between ANP and renin. Measurement of plasma ANP levels does not allow a differentiation between primary and secondary forms of hypertension. Elevated ANP levels are also found in primary hyperaldosteronism and in renal failure. Stimulation of ANP secretion by physical exercise and dietary salt loading is maintained in hypertension. Infusion of 1-28-hANP leads to a reduction in systemic arterial pressure in normotensives and hypertensives. The natriuresis induced by exogenous ANP is more pronounced in hypertensives. Stimulation of endogenous ANP secretion does not prevent the rise in blood pressure possibly due to a reduction in ANP receptors in target tissues.

Topics: Acromegaly; Animals; Atrial Natriuretic Factor; Humans; Hyperaldosteronism; Hypertension; Hypertension, Renal; Hypertension, Renovascular; Kidney Failure, Chronic; Male; Rats; Rats, Inbred Strains

Topics: Atrial Natriuretic Factor; Humans; Hyperaldosteronism; Hypertension; Natriuresis; Sodium, Dietary; Vasopressins; Water-Electrolyte Imbalance

Besides the classical modulators of aldosterone secretion, new factors influencing positively or negatively aldosterone secretion have been described. These new factors and the effect of related drugs constitutes the aim of this review. The effect of dopamine agonists and H2-receptor antagonists on aldosterone secretion in normal volunteers as well as in different clinical situations characterized by an increased production of aldosterone opens a new field of investigation for the therapy of aldosterone secretion alterations.

Topics: Aldosterone; Angiotensin II; Animals; Atrial Natriuretic Factor; Dopamine; Histamine; Humans; Hyperaldosteronism; Hypertension; Mineralocorticoid Receptor Antagonists; Pituitary Hormones; Potassium; Renin; Serotonin

Potassium depletion induced by dietary potassium restriction is known to cause sodium retention, while potassium supplementation is known to increase urinary sodium excretion. However, the ability of potassium deficiency to affect mineralocorticoid-induced sodium retention in aldosterone-producing adenoma (APA) subjects has not been extensively investigated, neither in baseline conditions nor when facilitating natriuresis through a physiological manoeuver such as central blood volume expansion. With the aim of testing the hypothesis that potassium supplementation would attenuate the mineralocorticoid-induced sodium retention, in 7 APA patients elevation of serum potassium was obtained by infusion of isosmotic potassium chloride (KCl) at a constant rate of 36 mmol/h for a 2-hour period for 5 consecutive days. The same patients were also submitted to acute central volume expansion by head-out water immersion (WI) associated with either low or normal serum potassium levels. The assessment of natriuresis in baseline condition and during WI was also performed in 10 age-matched control subjects. Central hypervolemia by WI induced a significant natriuretic response in APA hypokalemic subjects; on the other hand, in the same APA subjects giving potassium supplementation, WI-induced urinary sodium excretion was significantly higher (P <.001) than that obtained during WI at normal potassium intake (hypokalemic condition). Blood pressure responses and hormonal profiles were almost superimposable during the 2 WI experiments performed at different serum potassium levels. By confirming that amelioration of hypokalemia attenuates mineralocorticoid-induced sodium retention, this study also suggests that potassium intake may represent an important determinant of mineralocorticoid escape.

Topics: Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Diet; Dietary Supplements; Female; Humans; Hyperaldosteronism; Immersion; Male; Middle Aged; Natriuresis; Potassium Chloride; Renin; Sodium

We have previously shown that a bolus injection of alpha-human atrial natriuretic peptide (alpha-h-ANP) (100 micrograms) in patients with primary aldosteronism induces a transient decrease of blood pressure and a marked natriuresis, but no changes in plasma aldosterone levels. Eight additional cases were studied with a different protocol. Alpha-h-ANP was infused at the dose of 50 ng/kg/min over 1 h, after a bolus of 50 micrograms; saline alone was infused as control. Blood pressure, heart rate, plasma aldosterone, plasma renin activity, cortisol, serum and urinary Na and K and urinary volume were measured. A slight fall in blood pressure, without heart rate changes, was obtained within the first 5 min; this lasted throughout the infusion and for 1 h afterwards. Urinary volume and urinary sodium were significantly higher than controls during the first 2 h, while urinary potassium slightly increased only during the first hour. Plasma renin activity remained suppressed. Plasma aldosterone levels were similar throughout the infusion. Cortisol was not significantly different than placebo except that there was a significant rise after stopping ANP. These data confirm the potent natriuretic effect of ANP infusion and the lack of correlation between ANP induced natriuresis and the effect of ANP on aldosterone in patients with primary aldosteronism.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Female; Hemodynamics; Humans; Hydrocortisone; Hyperaldosteronism; Injections, Intravenous; Kidney; Male; Middle Aged; Potassium; Sodium

Whether atrial natriuretic factor (ANF) plays a physiological role in primary aldosteronism has yet to be determined. In the present study, the renal, hemodynamic, humoral, and vascular effects of a synthetic (WY-47663) human analogue were studied in five water-loaded (15 ml H2O/kg) patients with adenomatous primary aldosteronism, a salt-sensitive, low renin, volume-expanded syndrome. ANF was infused for 3 hours at a low rate (0.005 micrograms/kg/min), which approximately doubled circulating immunoreactive ANF. Glomerular filtration rate and renal blood flow (inulin and para-aminohippurate clearance) remained stable, but sodium excretion increased significantly suggesting a dissociation between renal hemodynamics and natriuresis as well as a direct inhibitory effect on tubular sodium reabsorption by ANF. Intra-arterial diastolic blood pressure, heart rate, forearm blood flow (plethysmographic method), and arterial plasma norepinephrine did not change, but systolic blood pressure declined and hematocrit rose suggesting plasma volume contraction by ANF. Plasma aldosterone levels were unchanged indicating a loss of ANF-mediated aldosterone inhibition, possibly related to qualitative or quantitative alterations of ANF receptors in tumoral adrenal tissue. Infusion of the analogue into the brachial artery was at a rate of 0.005 micrograms/dl forearm tissue/min x 30 minutes, which also doubled local immunoreactive venous ANF concentrations and vasodilated forearm arterioles. These data suggest a physiological role for ANF in modulating body fluid volume even in human primary aldosteronism.

Topics: Adult; Atrial Natriuretic Factor; Female; Hematocrit; Hemodynamics; Humans; Hyperaldosteronism; Kidney; Male; Middle Aged

To measure the plasma concentrations of adrenomedullin (ADM),atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP), and investigate their pathophysiological functions in patients with primary aldosteronism (PA). Between June 2006 and December 2012, we recruited 25 patients with untreated PA, 30 patients with untreated low-renin essential hypertension (EH), and 35 healthy control subjects. The plasma concentrations of ADM, ANP, and BNP were measured in all the subjects. After 4 weeks of effective antihypertensive therapy with slow-release nifedipine, the three peptides were measured again in the PA and low-renin EH subjects. Unilateral laparoscopic adrenalectomy was performed in all the PA patients; 2 weeks after surgery, the three peptides were measured again. The PA patients had significantly higher plasma concentrations of ADM, ANP, and BNP than the low-renin EH and control subjects. The low-renin EH and control subjects significantly differed in the concentrations of the three peptides between low-renin EH and control subjects. ADM was the most important peptide associated with aldosterone or blood pressure in the PA patients. Plasma ADM concentration was not only correlated with plasma aldosterone concentrations, but also with systolic and diastolic blood pressures, and plasma ANP and BNP concentrations in the PA patients. By contrast, ADM concentration was not related to blood urea nitrogen levels, serum creatinine levels, and glomerular filtration rates. After antihypertensive treatment, the concentrations of the three peptides significantly decreased in the low-renin EH patients, but remained unchanged in the PA subjects. However, these concentrations significantly decreased 2 weeks after laparoscopic adrenalectomy in the PA subjects. ADM, ANP, and BNP possibly participate in the mechanisms counteracting further elevation of blood pressure or plasma volume expansion resulting from aldosterone hypersecretion in PA patients. An ADM/aldosterone local regulatory mechanism may be involved in regulating adrenal adenoma functions.

Topics: Adrenalectomy; Adrenomedullin; Adult; Atrial Natriuretic Factor; Essential Hypertension; Female; Humans; Hyperaldosteronism; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nifedipine; Vasodilator Agents

To monitor changes in the maternal renin-angiotensin-aldosterone system following laser therapy and amnioreduction in severe twin-to-twin transfusion syndrome (TTTS).. Observational prospective study.. Single university hospital in Poissy, France.. Sixty cases of TTTS at 16-26 weeks of gestation.. Maternal blood sampling before, 6 and 24 hours following the procedure.. Plasma levels of aldosterone, renin, angiotensin II (AII), atrial natriuretic peptide (ANP), vasopressin, sodium, potassium and plasma proteins together with full blood count were measured before, 6 and 24 hours following the procedure.. TTTS is associated with maternal hyperaldosteronism dissociated from renin-angiotensin changes. Correcting TTTS by placental surgery and amnioreduction triggers incomplete correction of hyperaldosteronism, as early as 6 hours following the procedure, without changes in AII but an increase in the levels of ANP in plasma. Electrolyte concentrations remained stable despite haemodilution, while vasoactive hormone levels such as that of vasopressin remained unchanged.. Mechanisms involved in marked fluid retention in TTTS are rapidly corrected by laser therapy followed by amnioreduction while maintaining electrolyte homeostasis.

Topics: Adult; Analysis of Variance; Atrial Natriuretic Factor; Female; Fetofetal Transfusion; Hematocrit; Hemoglobins; Humans; Hyperaldosteronism; Laser Therapy; Plasma Substitutes; Pregnancy; Pregnancy Complications; Pregnancy Reduction, Multifetal; Pregnancy Trimester, Second; Pregnancy, Multiple; Renin; Vasopressins

The purpose of this study is to evaluate the relationship between aldosterone and blood pressure in a total of 220 normotensive and 293 essential hypertensive subjects in 2 genetically distinct populations-blacks and white French Canadians. The 24-hour blood pressure monitoring was performed under standardized conditions after discontinuing antihypertensive medications. Plasma renin activity and plasma aldosterone were measured in the supine position and after standing for 10 minutes. Plasma atrial natriuretic factor was also measured. Supine and standing plasma renin activities were lower (P< or =0.01), plasma aldosterone was higher (P<0.0001), and the aldosterone/renin ratios were higher (P<0.0001) in the hypertensive subjects. Atrial natriuretic factor was also higher in the hypertensive subjects (P<0.0001). Among blacks, blood pressures did not correlate with plasma renin activity. However, both average daytime and nighttime systolic and diastolic blood pressures were correlated with supine and standing plasma aldosterone and with the aldosterone/renin ratio (P<0.005 or less). In French Canadians, blood pressures tended to be positively correlated with standing plasma renin activity and aldosterone, but not with the aldosterone/renin ratio. Correlations of blood pressure with aldosterone were more consistent and more striking in blacks than in French Canadians. In both ethnic groups, there were inconsistent correlations of blood pressure with atrial natriuretic factor. These observations are consistent with the hypothesis that aldosterone-induced volume expansion is an important contributor to hypertension, especially in blacks.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Black People; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Case-Control Studies; Female; Humans; Hyperaldosteronism; Hypertension; Male; Middle Aged; Renin; White People

Atrial and brain natriuretic peptides (ANP and BNP, respectively) are cardiac hormones with natriuretic and vasodilator actions. The present study was carried out to determine the natriuretic peptide that is closely related to cardiac load and volume retention in patients with primary aldosteronism (PA).. We examined 11 patients with PA due to aldosterone-producing adrenal adenoma before and after surgical resection. Plasma levels of ANP and BNP were measured by specific immunoradiometric assays, and total blood volume was determined by a plasma tracer method with (131)I-human albumin.. Plasma levels of ANP and BNP were elevated in the PA patients compared with normotensive control subjects (P < .01), and the elevated ANP and BNP levels were reduced (P < .01) after adenoma resection. When analyzed with the pre- and postoperative data, a significant relationship was observed between mean blood pressure and plasma levels of ANP (r = 0.64, P < .01) and BNP (r = 0.58, P < .01). The BNP was significantly correlated with the SV1 + RV5 voltage (r = 0.65, P < .01) and with total blood volume (r = 0.57, P < .01), but this was not the case for ANP.. The present results suggest that the plasma level of BNP is more closely related to cardiac load or volume status than ANP is, in patients with PA due to adrenal adenoma.

Topics: Adenoma; Adrenal Gland Neoplasms; Adult; Atrial Natriuretic Factor; Biomarkers; Blood Volume; Cardiac Volume; Female; Humans; Hyperaldosteronism; Male; Middle Aged; Natriuretic Peptide, Brain

Normotensive primary hyperaldosteronism is exceedingly rare. We report two new cases of this syndrome in two middle-aged women, one of Asian origin. The presenting signs were tetany in one case and an adrenal mass in the other. Neither patient had hypertension, despite repeated measurements with a manual armlet. A typical biological profile of primary hyperaldosteronism was demonstrated in both patients, including hypokalemia with inappropriate kaliuresis, elevated resting plasma aldosterone, and undetectable plasma renin activity. The circadian rhythm of blood pressure was studied by ambulatory monitoring pre- and post-operatively. It confirmed the lack of hypertension, but the circadian rhythm of blood pressure was lost before surgery in one patient. Surgical removal of the histologically typical aldosterone-producing adenomas normalized the kalemia. The main finding in these two patients was spontaneously low blood pressure in the post-operative period. This suggests that excess aldosterone induced relative hypertension in these patients whose blood pressure was spontaneously very low. Genetic screening for dexamethasone-sensitive hyperaldosteronism was negative in both patients.

Topics: Adenoma; Adrenal Gland Neoplasms; Adult; Aldosterone; Atrial Natriuretic Factor; Blood Pressure Monitoring, Ambulatory; Blotting, Southern; Chromatography, High Pressure Liquid; Dexamethasone; Female; Gas Chromatography-Mass Spectrometry; Humans; Hyperaldosteronism; Hypertension; Potassium; Radioimmunoassay; Renin; Tetany; Tomography, X-Ray Computed

The release of arginine vasopressin (AVP) and atrial natriuretic hormone (ANH) and their involvement in renal water and electrolyte metabolism in primary aldosteronism in humans were studied. An oral acute water load (20 ml/kg body weight) was given to each of 12 patients before and after surgical removal of their aldosterone-producing adenoma(s). Plasma AVP and ANH were measured simultaneously, and renal water and electrolyte metabolism and tubular functions were determined. The same water load was given to seven normal subjects and the same parameters were determined. In the presence of mineralocorticoid excess before the operation, plasma AVP was relatively low compared with plasma osmolality (Posm), but was not suppressed in response to decreases in Posm after the water load. Baseline plasma ANH was high and increased further after the water load; urinary dilution and diuresis both remained normal. After the operation, baseline plasma AVP was normal and decreased in response to the decrease in Posm after the water load, with normal urinary dilution and diuresis. Baseline plasma ANH was normal, and did not increase after the water load. The ratio of urinary K and Na clearances and distal tubular reabsorption of Na increased before the operation. These results suggest that there are perturbations of AVP and ANH release in primary aldosteronism, despite the normal urinary dilution after a water load.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenalectomy; Adult; Aged; Arginine Vasopressin; Atrial Natriuretic Factor; Blood; Drinking; Female; Humans; Hyperaldosteronism; Male; Middle Aged; Natriuresis; Osmolar Concentration; Postoperative Period; Potassium; Time Factors; Urine; Vasopressins

We investigated renal and peripheral forearm extraction of atrial natriuretic peptide in patients with primary aldosteronism to determine whether alterations in extraction may contribute to the elevated levels of circulating atrial natriuretic peptide observed in primary aldosteronism. We obtained simultaneous venous blood samples from the left renal vein and a peripheral vein and from the radial artery in 28 patients with primary aldosteronism and 10 patients with essential hypertension. Renal extraction of atrial natriuretic peptide was significantly (P < .001) reduced (40 +/- 2%) in primary aldosteronism compared with essential hypertensive patients (62 +/- 3%). Peripheral forearm extraction was also reduced (P < .01) in primary aldosteronism compared with essential hypertensive patients (24 +/- 3% versus 38 +/- 4%). These findings are consistent with widespread downregulation of atrial natriuretic peptide receptors in primary aldosteronism. Consistent with reports that marked reduction in glomerular filtration rate is required before the renal extraction of atrial natriuretic peptide is reduced, no significant relationship between renal extraction of atrial natriuretic peptide and plasma creatinine was seen in primary aldosteronism or essential hypertension. Although the major regulators of atrial natriuretic peptide secretion in primary aldosteronism are presumably alterations in arterial blood pressure and plasma volume, reduced renal and peripheral extraction of atrial natriuretic peptide in primary aldosteronism may also contribute significantly to the elevated circulating levels observed.

Topics: Arteries; Atrial Natriuretic Factor; Forearm; Humans; Hyperaldosteronism; Kidney; Renal Circulation; Veins

The present study was designed to determine whether brain natriuretic peptide (BNP) is synthesized in the human adrenal gland and, if so, to investigate the BNP content of adrenal tissue and the changes in BNP messenger ribonucleic acid (mRNA) in patients with primary aldosteronism. A considerable amount of BNP-like immunoreactive substances was extracted from the adrenal glands of kidney donors for transplantation (0.21 +/- 0.02 pmol/g wet tissue; n = 3) and the remnant nontumorous adrenal glands of patients with primary aldosteronism (0.20 +/- 0.05 pmol/g wet tissue; n = 3; mean +/- SEM). Immunohistochemical study with a specific antihuman BNP antibody revealed that BNP-like immunoreactivity was localized in the adrenal medullary area, and an in situ hybridization study indicated that the BNP mRNA was mainly expressed in the cells of adrenal medulla. Using a reverse transcription and polymerase chain reaction technique, BNP complementary DNA was cloned from the human adrenal gland, and the sequence was identical to that of BNP identified in the atria. The level of BNP mRNA in the adrenal glands of patients with primary aldosteronism (n = 4) was obviously elevated compared to that in the kidney donors (n = 4), as determined by Northern blot analysis. Quantitative polymerase chain reaction measurements of BNP and atrial natriuretic peptide (ANP) mRNAs showed that both of the adrenomedullary natriuretic peptide gene transcriptions were enhanced in patients with primary aldosteronism, but the amount of ANP mRNA was far higher than that of BNP mRNA in the human adrenal gland. Our results are the first to indicate that BNP is synthesized in the human adrenal medulla, and that such medullary BNP synthesis increases in patients with primary aldosteronism. These facts support the proposal that adrenomedullary BNP along with ANP may play some role in water and electrolyte homeostasis or act in a paracrine manner to regulate adrenocortical functions.

Topics: Adrenal Medulla; Adult; Atrial Natriuretic Factor; Base Sequence; Blotting, Northern; DNA, Complementary; Humans; Hyperaldosteronism; Immunohistochemistry; In Situ Hybridization; Male; Molecular Sequence Data; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Polymerase Chain Reaction; Radioimmunoassay; RNA, Messenger

Primary aldosteronism is an important, potentially curable, form of hypertension. We examined the possible association between restriction fragment length polymorphisms in the atrial natriuretic peptide (ANP) gene and responsiveness of aldosterone to angiotensin II in 59 patients with primary aldosteronism due to aldosterone-producing adenoma (APA). Significant differences in the allelic frequencies of the BglI, TaqI and XhoI polymorphic sites at the ANP gene locus (chromosome 1; 1p36) between angiotensin II-unresponsive and angiotensin II-responsive tumors were observed. Variation in the ANP gene between the two groups may result in altered expression of ANP within the adrenal gland, and may contribute to the biochemical regulation of aldosterone production of these two subgroups of patients with APA.

Topics: Adenoma; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Deoxyribonucleases, Type II Site-Specific; Genotype; Humans; Hyperaldosteronism; Polymorphism, Restriction Fragment Length

High level of urinary kallikrein excretion was observed in a 23-year-old man with primary aldosteronism. Unilateral adrenalectomy improved the clinical symptoms and normalized the urinary concentration of this vasoactive substance. Although plasma atrial natriuretic factor was not elevated, adrenal surgery lowered its concentration. Coexistence of an adrenal adenoma and lesions of nodular hyperplasia were detected in the removed adrenal gland. We summarize the clinical data of this patient and review the literature.

Topics: Adrenal Cortex; Adrenal Cortex Neoplasms; Adrenalectomy; Adrenocortical Adenoma; Adult; Atrial Natriuretic Factor; Humans; Hyperaldosteronism; Kallikreins; Male

To investigate the possible role of dopamine, a catecholamine with natriuretic properties, in modulating the escape from the sodium-retaining effects of mineralocorticoids, we submitted six aldosterone-producing adenoma (APA) patients and six low-renin essential hypertensive patients to acute volume expansion by head-out water immersion with or without dopaminergic blockade by metoclopramide. Water immersion alone induced a marked, comparable natriuresis (P < 0.001) in both hypertensive groups where a slight reduction of already suppressed renin-angiotensin system and a marked stimulation of atrial natriuretic peptide was also observed (P < 0.03 and P < 0.002, respectively). Water immersion plus dopaminergic blockade by metoclopramide did not significantly affect the natriuresis observed during water immersion alone in APA patients; conversely, there was a blunted natriuretic response in low-renin hypertensives during water immersion plus metoclopramide, in comparison with that obtained during water immersion alone (P < 0.006). Furthermore, metoclopramide did prevent the suppression of plasma aldosterone levels produced by central volume expansion alone in low-renin hypertensives, although it did not affect plasma aldosterone levels during water immersion in APA patients. Our data suggest that dopaminergic blockade does not counteract the natriuretic ability of the other hemodynamic and humoral mechanisms involved in the escape phenomenon of APA patients, thus casting serious doubt on the possible role of dopamine in mediating the escape from the sodium-retaining effects of mineralocorticoids.

Topics: Adenoma; Adult; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Creatinine; Dopamine; Female; Hemodynamics; Humans; Hyperaldosteronism; Hypertension; Immersion; Isotonic Solutions; Kidney; Male; Metoclopramide; Middle Aged; Mineralocorticoids; Potassium; Renin; Renin-Angiotensin System; Sodium; Sodium Chloride; Urination

The human heart secretes both atrial natriuretic peptide and brain natriuretic peptide. This study attempts to clarify the pathophysiological significance of the peptides in cardiovascular diseases. Using immunoradiometric assay, plasma brain natriuretic peptide and atrial natriuretic peptide levels in essential hypertension, various secondary hypertension, chronic renal failure, chronic heart failure during cardiac pacing, and acute myocardial infarction were determined. Mean plasma brain natriuretic peptide and atrial natriuretic peptide levels in healthy subjects were 3.7 +/- 0.3 and 5.7 +/- 0.3 pmol/L, respectively, and increased as a function of age. Plasma brain natriuretic peptide levels showed a larger increase than atrial natriuretic peptide levels in various cardiovascular diseases. In chronic renal failure, whereas plasma atrial natriuretic peptide levels decreased significantly after hemodialysis and were correlated with the changes in body weight, changes in plasma brain natriuretic peptide levels were less prominent and did not show such a correlation. In chronic heart failure, both basal plasma brain natriuretic peptide and atrial natriuretic peptide levels were also significantly elevated. However, in response to acute ventricular or atrial pacing, brain natriuretic peptide levels did not show any increase in contrast to the marked increase of atrial natriuretic peptide levels. In acute myocardial infarction, brain natriuretic peptide levels showed more prominent changes than atrial natriuretic peptide levels and were correlated with serum levels of creatine kinase and cardiac myosin light chain I in most patients. These results suggest that both brain and atrial natriuretic peptides play an important role in the regulation of cardiovascular homeostasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenal Gland Neoplasms; Adult; Aged; Aging; Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Cardiovascular Diseases; Female; Heart Failure; Humans; Hyperaldosteronism; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Pheochromocytoma; Reference Values; Regression Analysis; Renal Dialysis

We had a 20-year-old male patient of secondary aldosteronism similar to Bartter's syndrome, which had proved to be evident after the remission of nephrotic syndrome. In the patient, hypokalemic alkalosis and hyperreninemic hyperaldosteronemia were observed, although the blood pressure was normal. Hyperplasia of juxtaglomerular cells was observed and no abnormalities indicating either glomerulonephritis or renal artery stenosis were found; the pressor response to intravenously infused angiotensin (ang) II was markedly decreased; urinary prostaglandin (PG) E2, kallikrein and kinin excretion were elevated. The inhibition of PG synthesis with indomethacin decreased renal PG production and partially corrected both hypokalemia and pressor responsiveness to ang II. Thus, this case is considered to be a case of Bartter's syndrome. Contrary to the previously reported observations, the effective fractional chloride reabsorption rate in the renal distal tubules was normal (> 80%) and not changed by PG inhibition. Plasma atrial natriuretic peptide level was normal. An interaction between renin-angiotensin and PG systems appears to play a prior role in this case. To explain the pathophysiology, we have hypothesized an abnormal function of ang II receptor signal transduction which excessively stimulates PLA2, resulting in overproduction of PG synthesis in tissues.

Topics: Adult; Angiotensin II; Atrial Natriuretic Factor; Bartter Syndrome; Captopril; Chlorides; Cyclooxygenase Inhibitors; Dextrans; Humans; Hyperaldosteronism; Kidney; Kidney Tubules, Distal; Male; Nephrotic Syndrome; Prostaglandin Antagonists; Water-Electrolyte Balance

The present study was designed to determine whether atrial natriuretic polypeptide (ANP) is synthesized in the human adrenal gland and, if so, to investigate the ANP content of adrenal tissue and the ANP mRNA changes in patients with primary aldosteronism. A considerable amount of human alpha ANP-like immunoreactive substances was extracted from the remnant adrenal glands of three patients with primary aldosteronism (1.44, 1.0, and 0.77 pmol/g wet tissue; mean +/- SD, 1.07 +/- 0.28 pmol/g) and the adrenal glands of three kidney donors for transplantation (0.93, 0.58, and 0.27 pmol/g wet tissue; mean +/- SD, 0.59 +/- 0.27 pmol/g). High performance gel permeation chromatographic analysis coupled with a RIA of the tissue extract showed that the molecular form of ANP in the adrenal gland was the precursor form, i.e. human gamma ANP. An in situ hybridization study using an ANP cRNA probe indicated that the ANP mRNA was localized mainly in the medullary area of the gland. Northern blot analysis, using ANP cDNA as a probe, detected ANP mRNA in the adrenal gland. Furthermore, the level of ANP mRNA in the adrenal glands of patients with primary aldosteronism was obviously elevated compared to that in the kidney donors. Our results were the first to indicate that ANP is synthesized in the human adrenal medulla, and such medullary ANP synthesis increases in patients with hypermineralocorticoidism. These facts support the proposal that extraatrial (medullary) ANP synthesis might act in a paracrine or endocrine manner to regulate water and electrolyte homeostasis.

Topics: Adrenal Glands; Adrenal Medulla; Adult; Atrial Natriuretic Factor; Blotting, Northern; Humans; Hyperaldosteronism; In Situ Hybridization; Male; Rest; RNA, Messenger; Supination

Topics: Atrial Natriuretic Factor; Humans; Hyperaldosteronism; Hypertension; Renal Circulation; Renin; Sodium

Atrial natriuretic peptide (ANP) can be elevated in conditions which are characterized by increased atrial pressure and or expanded plasma volume. We and others have previously shown a significant increase of ANP plasma levels in a small number of patients with primary aldosteronism. In this study we have extended the assay of plasma ANP to a larger number of patients. We studied ANP plasma levels before and after upright posture and acute sodium load in 16 patients with aldosteronoma (APA) and 13 with idiopathic aldosteronism (IHA). The study was repeated also after the removal of aldosteronoma. In patients with primary aldosteronism, the mean supine ANP plasma level was significantly higher than in the age matched normal subject group; supine ANP was significantly higher in the APA than in the IHA group. The decrease of ANP levels after upright posture was significant in both groups. The ANP increase after acute saline load was similar in APA and in IHA. After the removal of aldosteronoma ANP values returned to normal. In conclusion, it is confirmed that plasma ANP levels are elevated in primary aldosteronism and could reflect a greater volume expansion in patients with APA. Despite this difference, ANP still responds to physiological stimuli in both groups. Finally, ANP measurement can provide an additional tool in the differential diagnosis between APA and IHA.

Topics: Adenoma; Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Diagnosis, Differential; Female; Humans; Hyperaldosteronism; Male; Middle Aged; Osmolar Concentration; Posture; Renin-Angiotensin System; Sodium Chloride

To elucidate the factors which contribute to the exaggerated natriuresis in primary aldosteronism, hemodynamic and hormonal changes induced by saline infusion (at a rate of 0.5 l/h for 3 h) were examined in 6 patients with primary aldosteronism, 13 with essential hypertension, and 8 normotensive subjects. After saline infusion, increases in urinary sodium excretion, glomerular filtration rate, atrial natriuretic hormone, and urinary dopamine excretion along with suppression of plasma renin activity and aldosterone were compared in the three groups. All three groups demonstrated similar increases in glomerular filtration rate, but patients with primary aldosteronism did not show changes in urinary dopamine excretion, plasma renin activity, and aldosterone, despite their increased excretion of sodium. The increase in plasma atrial natriuretic hormone was significantly greater in primary aldosteronism than in essential hypertension or normotensive subjects. No changes in blood pressure or heart rate were seen. These findings suggest that atrial natriuretic hormone might play a role in the exaggerated excretion of sodium in patients with primary aldosteronism.

Topics: Aldosterone; Atrial Natriuretic Factor; Dopamine; Glomerular Filtration Rate; Humans; Hyperaldosteronism; Hypertension; Natriuresis; Norepinephrine; Plasma Volume; Renin; Sodium

Human adrenal gland and aldosterone-producing adenoma (APA) obtained from adrenalectomy could be maintained in vitro for one to two months. The explants continued to secrete aldosterone for the duration of culture. This method was superior to monolayer cell culture. The influence of alpha-human atrial natriuretic factor (alpha-hANF) was investigated by treating cultures of normal adrenal cortex and APA with alpha-hANF (10(-8) mol/L and 3 x 10(-8) mol/L respectively). We measured aldosterone in culture media collected at 2h before alpha-hANF treatment and 0.5, 2, 4 and 24h after. It was found that alpha-hANF stimulated aldosterone secretion of normal adrenal tissue but slightly inhibited that of APA.

Topics: Adenoma; Adrenal Cortex; Adrenal Cortex Neoplasms; Adult; Aldosterone; Atrial Natriuretic Factor; Culture Techniques; Female; Humans; Hyperaldosteronism; Male; Middle Aged

Plasma levels of atrial natriuretic peptide (ANP) were measured in patients with normal renin essential hypertension (n = 12), low renin essential hypertension (n = 11) and primary aldosteronism due to aldosterone producing adenoma (APA, n = 8) and idiopathic hyperaldosteronism (IHA, n = 3) after overnight rest in the supine position and after 4 h upright posture and furosemide administration. Plasma renin activity (PRA) and aldosterone (Aldo) levels were also determined. Compared to normal renin essential hypertension (33.6 +/- 2.2 pg/ml), basal plasma ANP was significantly higher in low renin essential hypertension (66.8 +/- 6 pg/ml), IHA (54.1 +/- 6.3 pg/ml) and APA before (62.4 +/- 4.9 pg/ml) but not after adrenal surgery (22 +/- 3 pg/ml). After upright posture and furosemide administration plasma ANP was decreased (p less than 0.01) in patients with low renin and, less markedly, with normal renin essential hypertension, however not in IHA and APA. In about half of the patients with low renin essential hypertension, unchanged PRA after upright posture and furosemide administration was associated with increased plasma Aldo and decreased ANP levels. We conclude that (i) the relatively high basal plasma ANP levels in low renin essential hypertension, IHA and APA may reflect the presence of volume expansion in these patients; (ii) the hormonal responses to upright posture and furosemide administration in patients with normal and low renin essential hypertension may indicate a counterregulatory role of ANP during activation of the renin-angiotensin-aldosterone system; (iii) the high plasma ANP, which is unresponsive to upright posture and furosemide administration, in patients with APA and IHA may be a potentially interesting new finding whose pathophysiological significance remains to be established.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Furosemide; Humans; Hyperaldosteronism; Hypertension; Middle Aged; Posture; Renin

Topics: Adenoma; Adrenal Gland Neoplasms; Adult; Aged; Atrial Natriuretic Factor; Female; Humans; Hyperaldosteronism; Male; Middle Aged

The effects of the alpha-human ANF and angiotension II on aldosterone secretion in vitro from cultured human adrenal tissues and the aldosterone-producing adenoma (APA) tissues were studied. The fresh human normal adrenal and APA tissues were obtained surgically from five patients. The tissues were mined 1.0 mm3 with scissors, put in DMEM containing 0.25% trypsin, and digested at 37 degrees C for 10 min. Then the tissues were washed with DMEM. The tissues were incubated in 4 ml DMEM containing 10% fetal calf serum at 37 degrees C under 5% CO2 in air for seven days and the aldosterone levels of the culture medium were determined by radioimmunoassay (RIA). The experiments were started on the tenth to fiftieth day of culture. The results show that the effect of alpha-human ANF (10(-8) mol/L final concentration) on aldosterone secretion from normal adrenal tissues was increased at 30 min following a decrement, but do not inhibit the aldosterone secretion in APA tissues. The aldosterone of short duration was inhibit by alpha-human ANF (3 x 10(-8) mol/L or 5 x 10(-8) mol/L) and the aldosterone secretion in a dose-dependent manner in the adenoma tissues. The aldosterone responses were not stimulated by angiotensin II (10(-9) mol/L) in normal adrenal and adenoma tissues, but angiotensin II (5 x 10(-9) mol/L) can stimulate APA tissues. Our results indicate the lack of effect of alpha-human ANF and angiotensin II on APA tissues could be due to the absence of receptors or a variance of the receptors, and/or the enzymes of steroidogenesis were abnormal. These tissues had a marked aldosterone response to ANF and angiotensin II during culturing in one month.

Topics: Adenoma; Adrenal Gland Neoplasms; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Culture Techniques; Humans; Hyperaldosteronism

Primary aldosteronism is the principal disorder of the zona glomerulosa, and a number of subsets have been identified: unilateral adenoma, bilateral micro- or macronodular hyperplasia (idiopathic aldosteronism), primary hyperplasia, and aldosterone-producing carcinoma, either adrenal or ectopic. The diagnostic criteria for a correct differential diagnosis of these subsets are now quite reliable, and our experience is presented in detail. Unfortunately, the pathogenesis of most of these forms is still poorly recognized and requires further investigation. An extreme sensitivity to angiotensin II is present in patients with idiopathic aldosteronism, and a role of adrenal renin is now being advocated. A peculiar form of hyperaldosteronism is the glucocorticoid-remediable subtype. An unusual sensitivity of aldosterone to ACTH is present in this form. The qualitative biochemical abnormality in this disorder consists of a marked overproduction of products of the cortisol C-18-oxidation pathway, 18-hydroxycortisol and 18-oxocortisol, which are more abundant than aldosterone and 18-hydroxycorticosterone. A family with 3 affected sibs has been studied by our group. In other clinical situations, classical zona fasciculata mineralocorticoids (deoxycorticosterone [DOC], corticosterone, and their 18-hydroxy compounds) are secreted in excess. The hypertensive diseases of this zone are rare DOC-secreting tumors and two forms of congenital adrenal hyperplasia, the 11 beta-hydroxylase and 17 alpha-hydroxylase deficiency syndromes, which are identified by the presence of hypokalemia and suppressed renin activity. DOC is the only mineralocorticoid hormone (MCH) oversecreted in the 11-hydroxylase deficiency syndromes, while all ACTH-dependent MCH levels are very high in the 17-hydroxylase deficiency syndromes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenoma; Adrenal Cortex Neoplasms; Adrenal Gland Diseases; Adrenal Glands; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Dexamethasone; Diagnosis, Differential; Humans; Hyperaldosteronism; Hypertension; Mineralocorticoids; Potassium; Sodium

Plasma concentrations of atrial natriuretic factor and some vasoactive substances were determined in 8 patients with aldosterone-producing adenoma, 10 with idiopathic adrenal hyperplasia, 10 normotensive subjects and 12 patients with essential hypertension. Plasma atrial natriuretic factor concentration in patients with aldosterone-producing adenoma was the highest among the examined groups. Adrenal surgery reduced plasma concentrations of atrial natriuretic factor and aldosterone concomitant with the elevation in urinary sodium excretion, plasma renin activity and urinary sodium-to-potassium ratio. Withdrawal of trilostane (3 beta-hydroxysteroid dehydrogenase inhibitor) in patients with idiopathic adrenal hyperplasia increased plasma concentrations of atrial natriuretic factor and aldosterone, and decreased the urinary sodium-to-potassium ratio, plasma renin activity and urinary sodium excretion. However, reduced urinary sodium excretion following trilostane treatment returned to the control level successively despite the high levels of plasma atrial natriuretic factor and aldosterone. Acute infusion of saline remarkably increased plasma atrial natriuretic factor concentration in patients with idiopathic adrenal hyperplasia and aldosterone-producing adenoma. These results suggest that a high level of atrial natriuretic factor is a characteristic feature in patients with aldosterone-producing adenoma caused chiefly by the expansion of extracellular fluid volume, and circulating atrial natriuretic factor may contribute to regulation of the sodium escape phenomenon in patients with aldosterone-producing adenoma or idiopathic adrenal hyperplasia.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenal Glands; Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Female; Humans; Hyperaldosteronism; Hyperplasia; Male; Middle Aged; Natriuresis; Potassium; Renin

1. In Bartter's syndrome, atrial pressures were low, consistent with volume contraction, while atrial natriuretic peptide (ANP) levels were unexpectedly elevated. Infusion of normal saline increased both right atrial pressure (RAP) and ANP levels, while administration of prostaglandin inhibitors raised RAP, probably due to volume expansion, but ANP levels fell paradoxically. 2. In Gordon's syndrome, atrial pressures were unexpectedly low or normal despite volume expansion, while ANP levels were normal. Pressor infusions of angiotensin II either raised right and left atrial pressures (LAP) without increasing ANP, or increased ANP without increasing atrial pressures. 3. In these two syndromes, atrial pressures and ANP levels were poorly correlated, leading to the proposal that other regulators of ANP may be important.

Topics: Adenoma; Adolescent; Adrenal Gland Neoplasms; Adult; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Bartter Syndrome; Blood Pressure; Child; Child, Preschool; Cyclooxygenase Inhibitors; Female; Humans; Hyperaldosteronism; Infant; Infusions, Intravenous; Male; Middle Aged; Radioimmunoassay; Renin

Several studies demonstrated that aldosterone secretion, by bovine, rat and human glomerulosa cells, is inhibited in vitro by atrial natriuretic factor (ANF). This effect has also been investigated with conflicting results in cells taken from aldosterone-producing tumors. In the present study, atrial natriuretic factor has been tested on aldosteronoma cells obtained from 4 patients with primary aldosteronism. The cells were studied both with perfusion and incubation systems. Aldosterone secretion was stimulated by ACTH, angiotensin II and potassium with or without ANF 10 microM. In this study ANF lacked to inhibit either basal and stimulated aldosterone secretion, indicating some alterations of ANF-adrenal interaction in this syndrome.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Humans; Hyperaldosteronism; Perfusion; Potassium; Tumor Cells, Cultured

The pharmacological effects of synthetic alpha-human atrial natriuretic peptide (alpha-hANP) in patients with Cushing's syndrome and primary aldosteronism were compared with those in normal volunteers. An infusion of synthetic alpha-hANP at 0.1 microgram/kg per min for 20 min produced a maximal plasma hANP level of 800-1200 pg/ml in patients with Cushing's syndrome and primary aldosteronism, and in normal subjects. There were significant decreases in the mean blood pressure (-10 to -15 mmHg) in patients with Cushing's syndrome and primary aldosteronism, similar to those in normal subjects. The plasma cyclic 3'5'-guanosine monophosphate (cGMP) concentrations of both groups of patients were increased fivefold over the baseline level following the infusion. Infusion of synthetic alpha-hANP caused a greater increase in the rate of sodium excretion in patients with Cushing's syndrome and primary aldosteronism compared with normal volunteers. The plasma cortisol and aldosterone concentrations did not, however, significantly change during alpha-hANP infusion in either the patients with Cushing's syndrome or those with primary aldosteronism. As synthetic alpha-hANP has a potent hypotensive effect in hypertensive patients with Cushing's syndrome and primary aldosteronism, a significant reduction in blood pressure and natriuresis seems to occur without affecting adrenocortical steroidogenesis.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Cushing Syndrome; Cyclic GMP; Female; Humans; Hyperaldosteronism; Male; Middle Aged; Natriuresis; Peptide Fragments; Renin

To investigate the involvement of atrial natriuretic peptide (ANP) in secondary hypertension, we examined hormonal and renal responses to ANP infusion (0.025 microgram/kg/min) in 27 patients with renal parenchymal hypertension, 10 with primary aldosteronism, 8 with renovascular hypertension, and 15 normotensive subjects. The preinfusion plasma concentration of ANP was significantly higher in patients with renal parenchymal hypertension (120 pg/ml, p less than 0.01) and in patients with primary aldosteronism (98 pg/ml, p less than 0.05) than in the normotensive subjects (40 pg/ml), but it was not greater than in the patients with renovascular hypertension (73 pg/ml, NS). In the patients with renal parenchymal hypertension, plasma ANP correlated negatively with creatinine clearance (r = -0.76, p less than 0.001). Mean blood pressure (-5%, p less than 0.01) and plasma aldosterone (-40%, p less than 0.001) decreased to a similar degree in the four groups during ANP infusion. However, an increase in urinary sodium excretion caused by ANP was higher in the hypertensive than in the normotensive patients (+250% vs. +70%, p less than 0.01) and correlated positively with mean blood pressure during ANP infusion (r = 0.47, p less than 0.001). The removal of adenomas in the patients with primary aldosteronism significantly lowered both plasma levels of ANP and cyclic guanosine 2',3'-monophosphate and reduced an increase in sodium excretion during ANP infusion, whereas the responses of blood pressure and plasma aldosterone to ANP infusion were not altered by the operation. Thus, these results suggest that elevated ANP secretion and increased natriuretic responses to ANP may modify the blood pressure and body fluid volume status in some types of secondary hypertension.

Topics: Adrenal Gland Neoplasms; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Cyclic GMP; Hormones; Humans; Hyperaldosteronism; Hypertension, Renal; Hypertension, Renovascular; Kidney; Osmolar Concentration; Postoperative Period; Reference Values; Renin

Patients with untreated essential hypertension had significantly higher plasma atrial natriuretic factor (ANF) levels (92.9 +/- 12.9 pg/ml, mean +/- SE) than those of age-matched controls (37.8 +/- 6.0 pg/ml; p less than 0.01). Plasma ANF levels in essential hypertensive patients showed a significant positive correlation with mean arterial pressure (MAP; r = 0.46, p less than 0.05) and an inverse correlation with plasma renin activity (PRA; r = -0.43, p less than 0.05). Plasma ANF levels after medication showed significant correlation with the decrease in MAP (r = 0.565, p less than 0.05). Patients with primary aldosteronism had significantly higher plasma ANF levels (122.4 +/- 30.2 pg/ml, n = 8) than those of controls (p less than 0.05). The levels returned to normal after extirpation of adrenal tumors. The response of plasma ANF levels in patients with primary aldosteronism to volume expansion with infusion of 2 L of physiological saline in 2 hours was greater than in controls. Such exaggerated response disappeared after surgical treatment. Infusion of angiotensin II (Ang II; 20 ng/kg/min) or norepinephrine (200 ng/kg/min) for 30 minutes to normal volunteers (n = 5) resulted in a rise in MAP (24.9 +/- 3.3 and 15.8 +/- 4.4 mm Hg, respectively) and a twofold increase in plasma ANF level. Infusion of the Ang II antagonist [Sar1, Ile8]Ang II (600 ng/kg/min) for 30 minutes, resulted in a rise in MAP (18.8 +/- 2.1 mm Hg) and more than a twofold increase in plasma ANF level in patients with essential hypertension (n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenal Gland Diseases; Angiotensin II; Atrial Natriuretic Factor; Blood Pressure; Female; Humans; Hyperaldosteronism; Hypertension; Male; Middle Aged; Norepinephrine; Renin; Vasoconstriction

Topics: Adrenal Cortex Neoplasms; Adult; Atrial Natriuretic Factor; Blood Pressure; Heart Rate; Humans; Hyperaldosteronism; Middle Aged; Pituitary Hormones, Anterior

Atrial natriuretic factor (ANF) may be physiopathologically involved in several clinical conditions including human hypertension. However, few data are available regarding this putative hormone and its relationship to aldosterone, blood pressure, and vascular responsiveness to alpha-adrenergic receptor stimulation in primary aldosteronism, a volume-expanded, low-renin model of human hypertension. For this reason, the behavior of supine and upright plasma ANF as related to aldosterone, blood pressure, and forearm alpha-adrenergic sensitivity (plethysmographic technique) to intra-arterial norepinephrine infusion was studied in eight patients with primary aldosteronism (five with adenomas, three with hyperplasia) before and at the end of two sequential 1-week low (20 mmol/day) and high sodium (200 mmol/day) diet periods. Basal, predict ANF concentrations decreased and increased after low and high sodium intakes, respectively. Furthermore, highly significant postural ANF decrements after 1 hour of standing occurred with each diet, although they were lower after the low than after the high sodium diet. Plasma aldosterone, either supine or upright, was insensitive to dietary sodium manipulations, suggesting the absence of ANF-mediated control of aldosterone secretion in our patients. In spite of about twofold higher ANF concentrations during the high than during the low sodium diet, forearm vascular sensitivity to intra-arterial norepinephrine infusion did not change during the study. Furthermore, systemic arterial blood pressure rose to a highly significant extent after dietary sodium content was increased, thus casting doubt on a role for ANF as an endogenous long-term modulator of systemic blood pressure and peripheral alpha-adrenergic sensitivity in patients with primary aldosteronism.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Female; Forearm; Humans; Hyperaldosteronism; Male; Norepinephrine; Posture; Regional Blood Flow; Sodium, Dietary; Vascular Resistance

In order to explore the role of atrial natriuretic peptide (ANP) in Bartter's syndrome, five patients and five healthy controls matched for age and sex were studied. The study was designed to stimulate and suppress ANP secretion by manipulation of right atrial pressure with different body positions and mild volume expansion with saline. Other vasoactive hormones were also measured, and heart rate and blood pressure were recorded at 5-min intervals. Plasma ANP levels increased after head-down tilt and returned to baseline in the upright position. Infusion of saline failed to increase plasma ANP both in the control group and in four of the patients. No significant differences were found in plasma atrial natriuretic peptide concentrations between both groups. In view of previously reported elevated plasma ANP levels, Bartter's syndrome may be heterogeneous in this respect. Plasma renin activity was higher in the patients, but plasma aldosterone, adrenaline and noradrenaline were similar in both groups. Mean arterial blood pressure was similar in both groups, but rose significantly in the upright position in the control group only, while changes in heart rate were similar in both groups. We conclude that atrial natriuretic peptide does not seem to play a causal role in our patients with Bartter's syndrome.

Topics: Adult; Atrial Natriuretic Factor; Bartter Syndrome; Female; Hemodynamics; Humans; Hyperaldosteronism; Infusions, Intravenous; Male; Posture; Renin; Sodium Chloride

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenal Glands; Adult; Aldosterone; Atrial Natriuretic Factor; Female; Furosemide; Humans; Hyperaldosteronism; Hyperplasia; Isotonic Solutions; Male; Middle Aged; Radioimmunoassay; Sodium Chloride; Spironolactone

Using two radio-immunoassays for N-terminal and C-terminal fragments of human atrial natriuretic polypeptide (ANP) precursor, gamma-hANP [human atrial natriuretic factor-(1-126)], that is gamma-hANP(1-25) [human atrial natriuretic factor-(1-25)] and alpha-hANP [human atrial natriuretic factor-(99-126)], we studied the secretion of gamma-hANP-derived peptides into circulation from the heart in normal subjects and patients with essential hypertension and adrenal disorders. Volume expansion with 2 litres physiological saline increased plasma gamma-hANP(1-25)-like immunoreactivity concomitantly with plasma alpha-hANP-like immunoreactivity in normal subjects. Infusion of angiotensin II (20 ng/kg per min) or noradrenaline (200 ng/kg per min) also caused a parallel increase in plasma gamma-hANP(1-25)-like and alpha-hANP-like immunoreactivity. Plasma gamma-hANP(1-25)-like immunoreactivity levels were changed together with alpha-hANP-like immunoreactivity in patients with essential hypertension and adrenal disorders. These results indicate that gamma-hANP-derived peptides, alpha-hANP and the 10-k N-terminal fragment of gamma-hANP (N-peptide) are cosecreted from the heart and that the simultaneous measurement of N-peptide and alpha-hANP serves as an indicator of the cardiac endocrine function. The significance of N-peptide as a hormone must await further clarification.

Topics: Addison Disease; Adrenal Gland Diseases; Adrenal Gland Neoplasms; Angiotensin II; Atrial Natriuretic Factor; Blood Volume; Cushing Syndrome; Humans; Hyperaldosteronism; Hypertension; Immunoassay; Pheochromocytoma

Topics: Angiotensin II; Atrial Natriuretic Factor; Bartter Syndrome; Humans; Hyperaldosteronism; Hypertrophy; Hypokalemia; Juxtaglomerular Apparatus; Kallikreins; Kidney Tubules; Kinins; Prostaglandins

Topics: Adult; Atrial Natriuretic Factor; Bartter Syndrome; Female; Furosemide; Humans; Hyperaldosteronism; Indomethacin; Male; Substance-Related Disorders

The withdrawal effect of spironolactone treatment on natriuresis was studied in relation to atrial natriuretic peptide (ANP) in five patients with primary aldosteronism due to adenoma. The patients had been treated with spironolactone for 2-3 months before they were admitted. After admission, blood pressure, body weight, and urinary excretion of sodium were measured daily. Venous samples were obtained twice a week for measurements of plasma levels of ANP, plasma renin activity (PRA), and plasma concentrations of aldosterone (PAC), cortisol, and deoxycorticosterone. The study was performed for 7 days during the treatment with spironolactone and for 18 days after stopping the administration. Plasma volume was determined two times, during the control period and on the 13th day after stopping spironolactone. Urinary sodium excretion decreased initially and returned to the control levels successively. Body weight and plasma volume increased, and blood pressure rose steadily. PRA and the plasma concentrations of cortisol and deoxycorticosterone decreased significantly (P less than 0.05); however, high levels of PAC did not alter significantly. Plasma ANP levels increased significantly (P less than 0.05) from 26 +/- 4 pg/ml during the control period to 195 +/- 47 pg/ml on the 13th day after stopping spironolactone. The data of the urinary sodium excretion showed the escape from sodium-retaining effect of aldosterone, and this escape could be explained by the increase in plasma ANP. Furthermore, ANP might contribute to the decrease in cortisol and deoxycorticosterone in plasma because of the direct inhibitory action of ANP on steroidogenesis.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Desoxycorticosterone; Humans; Hydrocortisone; Hyperaldosteronism; Middle Aged; Mineralocorticoids; Natriuresis; Potassium; Renin; Spironolactone

Atrial natriuretic peptide (ANP), besides its diuretic and antihypertensive effects, exhibits an "in vitro" inhibitory action on aldosterone. In order to elucidate if these effects are present also "in vivo", we injected 100 micrograms of alpha-human ANP as a bolus in normal volunteers, low renin essential hypertensive subjects (LRH) and in patients with primary aldosteronism (PA). A transient hypotensive effect was seen in all patients, without significant variations of heart rate. The diuretic and saluretic effects of ANP were greater in hypertensive subjects, even in PA where endogenous ANP levels are known to be elevated. Plasma aldosterone values decreased significantly only in normal volunteers. In conclusion, in LRH and PA renal effects of ANP are not diminished, although its aldosterone-inhibiting properties are less evident than in normals.

Topics: Adolescent; Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Diuresis; Humans; Hyperaldosteronism; Hypertension, Renal; Middle Aged; Natriuresis; Renin

Atrial natriuretic peptide, a hormone secreted by the heart, is involved in salt and fluid homeostasis and also exerts an inhibitory effect on aldosterone production in vitro. In order to elucidate if this effect is also present in man, 6 normal volunteers, 5 low renin hypertensive patients (LRH) and 7 patients with primary aldosteronism (PA) have received 100 micrograms of alpha-h-Anp as bolus i.v. (The decrease in blood pressure was mild and transient in all groups, whereas a marked diuretic effect was observed in all hypertensives even in PA where high levels of endogenous ANP have been found. In normals we observed a significant decrease of plasma aldosterone values while in PA and LRH this effect was not evident. This phenomenon associated with a greater natriuretic effect in LRH and PA, as compared with normals, demonstrates the lack of the correlation between ANP-induced diuresis and aldosterone inhibiting properties.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Diuresis; Heart Rate; Humans; Hydrocortisone; Hyperaldosteronism; Hypertension; Kinetics; Male; Middle Aged; Peptide Fragments; Potassium; Renin; Sodium

Low-dose angiotensin II (ANG II) infusion raised plasma atrial natriuretic peptide (ANP) levels only when endogenous renin-angiotensin levels were low, as in aldosterone-producing adenoma. When plasma renin activity (PRA) levels rose tenfold following removal of the tumour, low-dose ANG II infusion no longer stimulated ANP, but fivefold higher doses did. Indomethacin lowered both PRA and ANP in Bartter's syndrome and in normal subjects. The effect of indomethacin on ANP is probably not direct, since it did not lower ANP in aldosterone-producing adenoma. Neither did it lower PRA in aldosterone-producing adenoma, and in most studies ANP and PRA moved in parallel, consistent with positive regulation of ANP by ANG II. When ANG II infusion stimulated ANP, it also raised blood pressure, which could therefore be mediating the effects of ANG II on ANP. However, both PRA and ANP are high in Bartter's syndrome, while blood pressure is normal or low, and indomethacin lowers PRA and ANP in Bartter's syndrome and in normal subjects without lowering the blood pressure. The relative importance of regulatory factors such as central blood volume/atrial pressure and ANG II level probably varies in different situations. In aldosterone-producing adenoma, a high central blood volume appears to over-ride the effect of a low ANG II level. In Bartter's syndrome a high ANG II level appears to over-ride the effect of low central blood volume.

Topics: Adenoma; Adolescent; Adrenal Cortex Neoplasms; Adult; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Bartter Syndrome; Blood Pressure; Child; Child, Preschool; Humans; Hyperaldosteronism; Indomethacin; Middle Aged; Renin

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

Topics: Adenoma; Adrenal Gland Neoplasms; Atrial Natriuretic Factor; Cushing Syndrome; Humans; Hyperaldosteronism; Pheochromocytoma; Pituitary Neoplasms

Urinary sodium excretion initially decreases when mineralocorticoid levels are increased, but if high plasma levels of hormone are maintained, sodium excretion rises to again equal sodium intake. To ascertain if atrial natriuretic peptide (ANP) plays a role in reestablishing sodium balance during mineralocorticoid ingestion, 0.3 to 0.5 mg per day of fludrocortisone were administered for 18 days to four healthy male subjects. The average daily intake of sodium was regulated at 180 +/- 2 meq. ANP levels rose from a mean of 91.7 +/- 13.0 pg/ml during the control week to 179.7 +/- 39.2 pg/ml during the final week on fludrocortisone (p less than 0.05). Urinary sodium excretion fell 27% immediately after fludrocortisone administration was initiated but returned to baseline levels in an average of 5 days. Levels of ANP, normalized for each subject to the mean of his control week values, correlated with the amount of sodium excreted in the subsequent 24 hours (p less than 0.05). Simultaneous with the rise in ANP values, levels of plasma renin activity (PRA) and aldosterone decreased. ANP concentrations throughout the study were inversely correlated with PRA and aldosterone levels (p less than 0.001 for both correlations). Values of serum osmolality and plasma arginine vasopressin did not change significantly during the study. The results obtained demonstrate that increased secretion of ANP is associated with escape from the sodium retaining effect of chronically high mineralocorticoid levels in man and suggest that ANP plays a prominent role in the mechanism of this escape.

Topics: Adult; Aldosterone; Arginine Vasopressin; Atrial Natriuretic Factor; Glomerular Filtration Rate; Humans; Hyperaldosteronism; Male; Mineralocorticoids; Osmolar Concentration; Potassium; Renin; Sodium

Using the immunoperoxidase method with specific antibody, we examined the presence of atrial natriuretic peptide (ANP) in adrenal tissues of a patient with primary aldosteronism and those derived from a patient with Cushing's syndrome. We found cells immunopositive for ANP in primary aldosteronism but not in Cushing's syndrome. In primary aldosteronism, we noted positively stained cells mainly but not exclusively in the adenomatous tissue. These results demonstrate for the first time the presence of immunoreactive ANP in adrenal tissues of a patient with primary aldosteronism and suggest that adrenal ANP may have potentially important impacts on aldosterone secretion in this disorder.

Topics: Adrenal Glands; Adult; Atrial Natriuretic Factor; Cushing Syndrome; Humans; Hyperaldosteronism; Immunohistochemistry; Male

Topics: Adenoma; Adrenal Gland Neoplasms; Atrial Natriuretic Factor; Bartter Syndrome; Humans; Hyperaldosteronism; Plasma Volume; Radioimmunoassay; Syndrome

Topics: Adult; Atrial Natriuretic Factor; Bartter Syndrome; Humans; Hyperaldosteronism; Male; Tetany

We investigated whether the gene for atrial natriuretic factor, a recently discovered peptide hormone with potent natriuretic, diuretic, and vasorelaxant properties, was pathogenetically linked to an uncommon but well-defined fluid and electrolyte disorder, Bartter's syndrome. Restriction fragment length polymorphisms in the atrial natriuretic factor gene were sought in a large kindred with six of 23 family members being affected. A Bgl II polymorphism, identified in two of 40 (5%) apparently normal subjects, was found in one of two first-generation family members. This polymorphism was also present in five of seven unaffected second-generation siblings but in only three of six affected siblings. The failure of the absence or the presence of the polymorphism to cosegregate with the disease clearly indicates that in this kindred, the gene for atrial natriuretic factor is not linked to Bartter's syndrome.

Topics: Atrial Natriuretic Factor; Bartter Syndrome; Female; Genes; Humans; Hyperaldosteronism; Male; Pedigree; Polymorphism, Genetic

A RIA for alpha-human atrial natriuretic peptide (alpha hANP) in plasma was developed and used to study the immunoreactive components secreted by the heart and circulating in peripheral venous plasma. The assay used [125I]diiodotyrosyl-alpha hANP, purified by high pressure liquid chromatography (HPLC), and a C-terminal-specific antiserum purchased from Peninsula Laboratories. Serial dilution curves of coronary sinus plasma samples were parallel with the standard curve, but significant nonparallelism was found in peripheral plasma samples of low immunoreactivity. When plasma was extracted using C-18 Sep-Pak cartridges, serial dilution curves from both coronary sinus and peripheral plasma samples were parallel to the standard curve. Although values for plasma samples assayed before and after extraction agreed closely (r = 0.99; n = 76), immunoreactive ANP in unextracted plasma was consistently greater (70-79 pmol/liter) than in extracts of plasma, suggesting non-specific interference by a component in plasma when assayed without extraction. Mean plasma immunoreactive ANP in 19 normal subjects consuming a normal salt intake was 14 +/- 1 (+/- SE) pmol/liter. In 5 normal men, increasing dietary sodium intake from 10 to 200 mmol sodium/day was associated with a 2-fold increment in ANP levels, and similar changes accompanied acute sodium loading using iv saline. Elevated values were found in patients with congestive heart failure (mean, 58 pmol/liter; range, 0-200; n = 9), chronic renal failure (mean, 118 pmol/liter; range, 30-290; n = 8), and primary aldosteronism (range, 32-90 pmol/liter; n = 3). HPLC and gel chromatographic analysis of the immunoreactive material found in coronary sinus plasma extracts showed that a large amount of the material eluted in the position of alpha hANP. A smaller quantity of immunoreactive material with a mol wt of about 1600 was also identified. Peripheral venous plasma extracts also contained several immunoreactive components, the largest amount of which corresponded to alpha hANP. The pattern of immunoreactive components in peripheral venous plasma, as identified by both gel chromotography and HPLC, was similar to that in coronary sinus plasma drawn during an active phase of hormone secretion. These findings indicate that the heart secretes alpha hANP or a closely similar peptide which is also present in peripheral venous plasma. Plasma immunoreactive ANP is responsive to sodium loading in normal man and is elevated in patients

Topics: Adult; Atrial Natriuretic Factor; Chromatography, Gel; Chromatography, High Pressure Liquid; Female; Heart Failure; Humans; Hyperaldosteronism; Iodine Radioisotopes; Isotope Labeling; Kidney Failure, Chronic; Male; Middle Aged; Radioimmunoassay; Sodium; Specimen Handling

Radio-immunoassay of atrial natriuretic peptide (ANP) and infusions of alpha-human ANP (alpha-hANP) have been used to study the secretion, metabolism, regulation and actions of ANP in man. Plasma immunoreactive ANP (irANP) was twice as high in arterial blood as in simultaneously sampled venous plasma from the femoral, hepatic and renal vein, but no arteriovenous difference was found across the lung. Analysis of plasma extracts by high performance liquid chromatography confirmed that alpha-hANP-like material was a major component in coronary sinus and peripheral arterial and venous plasma. In normal subjects, venous plasma irANP was increased by both acute and chronic sodium loads, and by exercise. The cardiac secretion of irANP, and peripheral venous levels, were markedly increased by atrial pacing in four patients investigated for arrhythmia. Plasma irANP concentrations were elevated in many patients with circulatory disorders, including chronic renal failure, congestive heart failure and during spontaneous tachyarrhythmias. Constant 60-min intravenous infusions of alpha-hANP increased urinary sodium excretion in normal subjects, under conditions of both high- and low-sodium intake, and selectively reduced plasma aldosterone concentrations. These effects were observed at the venous levels of plasma irANP found in some patients with circulatory disease. Taken together, the present studies suggest that ANP has important endocrine functions in human health and disease.

Topics: Aldosterone; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Chromatography, High Pressure Liquid; Female; Heart Failure; Humans; Hyperaldosteronism; Kidney Failure, Chronic; Natriuresis; Physical Exertion; Pregnancy; Radioimmunoassay

Plasma levels of ANP were measured in normal subjects and in three conditions associated with disturbed volume homeostasis. Levels of ANP were appropriately raised in seven patients with primary aldosteronism, and fell to normal following removal of an aldosterone-producing adenoma in six and dexamethasone treatment in one patient with glucocorticoid-suppressible hyperaldosteronism. The level of ANP in one patient with Gordon's syndrome (a condition associated with plasma volume expansion) was lower than in the patients with primary aldosteronism, both before and after saline infusion. This is consistent with reduced ANP responsiveness in this condition. responsiveness in this condition. Levels of ANP were inappropriately elevated in three patients with Bartter's syndrome (a condition with plasma volume contraction) and rose further during saline infusion. This is consistent with primary hypersecretion of ANP.

Topics: Adult; Atrial Natriuretic Factor; Bartter Syndrome; Humans; Hyperaldosteronism; Hyperkalemia; Hypertension; Male; Middle Aged; Plasma Volume; Syndrome

Topics: Atrial Natriuretic Factor; Bartter Syndrome; Child, Preschool; Humans; Hyperaldosteronism; Indomethacin; Male

Plasma levels of atrial natriuretic peptide (ANP) were measured in 9 patients with primary aldosteronism and 41 patients with essential hypertension (class I or II by WHO classification) using a specific and sensitive RIA. The mean plasma ANP concentration in patients with primary aldosteronism (mean +/- SEM, 67.1 +/- 10.8 pg/ml; n = 9) was significantly higher than that in healthy normotensive subjects (37.9 +/- 1.4 pg/ml; n = 108) or patients with essential hypertension (38.5 +/- 2.8 pg/ml; n = 41). During treatment with spironolactone, plasma levels of ANP declined in 6 of the 7 patients with primary aldosteronism, but no change occurred in the remaining patient who had cardiac enlargement of unknown etiology. The mean plasma ANP concentration in patients with essential hypertension, on the other hand, was not significantly different from that in normal subjects. These results indicate that plasma ANP levels are elevated in patients with primary aldosteronism, probably due to volume expansion, whereas no abnormality in ANP secretion exists in patients with uncomplicated essential hypertension.

Topics: Adult; Atrial Natriuretic Factor; Female; Humans; Hyperaldosteronism; Hypertension; Male; Middle Aged; Spironolactone

Plasma atrial natriuretic peptide (ANP) levels were inappropriately elevated in Bartter's syndrome, in contrast with appropriately low levels in patients with Addison's disease and bulimia, with similar hyper-reninaemia and volume contraction. Inappropriate overproduction of ANP in Bartter's syndrome may be important in the pathophysiology. Prostaglandin inhibitors cause sodium retention and might be expected to increase ANP levels, based on their volume effects. Surprisingly, therefore, both indomethacin and aspirin lowered elevated levels of ANP in Bartter's syndrome to normal, indomethacin achieving this within 24 h. Single doses of indomethacin and aspirin also lowered plasma ANP levels in normal subjects. Saline infusion in Bartter's syndrome increased already-elevated levels of ANP further. When repeated during indomethacin treatment, despite suppression of basal levels to normal, even higher levels were achieved in three of four subjects. These results are consistent with a role for prostaglandins in ANP release in man, but suggest that another mechanism is also operative. They may help to explain the variable renal effects of prostaglandin inhibition.

Topics: Addison Disease; Adolescent; Adult; Atrial Natriuretic Factor; Bartter Syndrome; Bulimia; Child; Child, Preschool; Humans; Hyperaldosteronism; Indomethacin; Middle Aged; Reference Values; Sodium Chloride