Plasma levels of atrial natriuretic hormone in Cushing's syndrome

To examine a possible role for atrial natriuretic hormone (ANH) in the water and electrolyte disturbances associated with hypercortisolism, plasma ANH levels were measured in 18 patients with endogenous Cushing's syndrome. Nine patients had elevated plasma ANH levels compared to normal subjects. The mean plasma ANH concentration [72.5 +/- 13.0 (+/- SE) pg/mL (23.5 +/- 4.2 pmol/L)] in the Cushing's syndrome patients was significantly higher than that in 40 normal subjects [37.6 +/- 1.9 pg/mL (12.2 +/- 0.62 pmol/L)]. A significant positive correlation was found between plasma ANH and cortisol levels in individual patients. There were no significant correlations, on the other hand, between plasma ANH concentrations and PRA, plasma aldosterone levels, or mean blood pressure. After treatment, plasma ANH concentrations decreased in all 6 patients who had elevated plasma ANH levels preoperatively. In 1 patient with Cushing's disease, plasma ANH levels changed in parallel with plasma cortisol concentrations during o,p'DDD treatment. Fifteen patients who were receiving long term synthetic glucocorticoid therapy for the treatment of miscellaneous diseases had a significantly higher mean plasma ANH level [50.2 +/- 4.0 (+/- SE) pg/mL (16.3 +/- 1.3 pmol/L)] than that in normal subjects. These results suggest that plasma ANH levels are elevated in a substantial number of patients with Cushing's syndrome due to either a direct stimulatory effect of glucocorticoid on atrial ANH secretion or, alternatively, intravascular volume expansion resulting from excessive cortisol secretion.     

Plasma atrial natriuretic peptide concentrations in patients weaning from positive-pressure ventilation.

The effect of positive-pressure ventilation on plasma atrial natriuretic peptide (ANP) concentrations was investigated in sixteen patients weaning from the ventilator. During spontaneous ventilation plasma ANP concentrations rose significantly from 59 (16-270) to 67 (13-320) pg/ml (median and range, P less than 0.05) and mean arterial blood pressure rose from 84 +/- 3 to 92 +/- 3 mmHg (mean +/- SEM, P less than 0.05) if compared with periods of positive-pressure ventilation. This increase in plasma ANP concentrations occurred irrespective of the underlying disease and the wide scatter of the ANP plasma levels found in individual patients. As right atrial stretch is the major stimulus for the release of the ANP the data indicate a decrease in cardiac output during positive-pressure ventilation following an impaired central venous return to the heart.     

Plasma atrial natriuretic peptide (ANP) in relation to blood pressure in severe hypertension.

Atrial natriuretic peptide-like immunoreactivity in plasma (ANP-LI) was studied in patients with severe hypertension (n = 21) and in matched healthy control subjects. There was no correlation between ANP-LI and blood pressure, and the distribution of ANP-LI values did not differ between the two groups. These results are consistent with the assumption that an increase in ANP is not caused by elevated blood pressure, although elevated ANP-LI may be found in subgroups of hypertensive subjects with increased atrial pressures due to, for example, cardiac failure.     

Plasma atrial natriuretic factor in isolated systolic hypertension in the elderly: response to hypertonic saline infusion.

Plasma immunoreactive atrial natriuretic factor (ANF) and urinary sodium excretion were measured in elderly patients with isolated systolic hypertension (ISH) (n = 11), age-matched essential hypertensive patients (EHT; n = 16) and normotensive subjects (NT; n = 9) before and during a 60 min infusion of hypertonic saline (120 mEq of Na+). An exaggerated natriuresis during the sodium load was observed only in ISH. Baseline plasma ANF levels in ISH were significantly lower (P less than 0.05) than those of EHT and NT. There was no significant change in plasma ANF in EHT and NT subjects after the saline load. In contrast, there was a significant increase in plasma ANF (P less than 0.05) after the saline load in ISH. The change in urinary sodium excretion was significantly correlated with the change in plasma ANF (r = 0.75, P less than 0.01) in ISH. We conclude that an exaggerated natriuresis during a hypertonic saline infusion may be linked to an increase in plasma ANF in elderly ISH patients.     

Plasma atrial natriuretic peptide in essential hypertension after treatment with irbesartan

The aim of this study was to evaluate the medium-term effects of the selective AT 1 -blocker irbesartan on atrial natriuretic peptide (ANP) levels in patients with moderate essential hypertension. The drug was given orally in a daily dose of 300 mg for 30 days. Plasma ANP levels increased by 15.7% despite the drop in blood pressure and the slight decrease of atrial and ventricular diameters. These findings indicate that AT 1 -blockers like irbesartan exert part of their antihypertensive action by increasing ANP plasma levels.     

Plasma levels of atrial natriuretic peptide in primary aldosteronism and essential hypertension

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.     

Plasma atrial natriuretic polypeptide concentrations during and after reversion of paroxysmal supraventricular tachycardias.

Plasma concentrations of immunoreactive atrial natriuretic polypeptide were raised in 22 of 23 patients with paroxysmal supraventricular tachycardia and in all seven patients with atrial flutter. Plasma concentrations of atrial natriuretic polypeptide rose soon after the onset of supraventricular tachycardia. A sample taken 30 minutes after reversion to sinus rhythm (pharmacological or non-pharmacological) showed a significant fall in 19 of the 23 patients with paroxysmal supraventricular tachycardia and all seven patients with atrial flutter. Because atrial natriuretic polypeptide has powerful natriuretic and diuretic properties, an increase may contribute considerably to the polyuria that is often associated with episodes of supraventricular tachycardia.     

Plasma atrial natriuretic hormone levels in patients with the syndrome of inappropriate antidiuretic hormone secretion

This study explored whether atrial natriuretic hormone (ANH) might be involved in the escape from salt and water retention that occurs in patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Sixteen patients with low serum Na+ concentrations [123 +/- 1 (+/- SE) mmol/L] were studied. Each patient excreted urine that was hyperosmolar (mean, 391 +/- 4 mosmol/kg) in relation to serum osmolality (mean, 258 +/- 4 mosmol/kg). Sodium excretion (81 +/- 20 mmol/L) also was inappropriate to the low serum Na+ level. The probable causes of SIADH were head trauma (4), pneumonia (5), lung cancer (3), and chlorpropamide therapy (4). In the nontumor patients, plasma and/or urinary vasopressin (AVP) concentrations were in the normal range, but inappropriate for serum osmolality. Urinary AVP values of 50 pg/mL or more (greater than 46 pmol/L) were found in the three tumor patients. The mean plasma ANH concentration was 6-fold higher than that in normal subjects [296 +/- 51 vs. 51 +/- 13 pg/mL (100 +/- 20 vs. 17 +/- 4 pmol/L); P less than 0.01]. Six SIADH patients were studied again after brief (1-3 days) water restriction. Although serum osmolality increased in each, their plasma AVP concentrations decreased very little, and urinary AVP excretion and plasma ANH did not change. These results indicate that plasma ANH levels are markedly increased in patients with SIADH. Their increased ANH secretion may antagonize water retention resulting from the inappropriate AVP secretion.     

Low atrial natriuretic peptide plasma concentrations in 100 patients with essential hypertension

Although atrial natriuretic peptide (ANP) plays a key role in electrolyte and volume regulation and causes direct vasorelaxation, controversial results have been reported in hypertensive patients. We studied 58 men and 42 women, aged 19 to 78 years, with essential hypertension (blood pressure: 150 to 210/95 to 110 mm Hg) using 24 h blood pressure recording, treadmill exercise and x-ray of the chest. In 70 patients ANP plasma concentrations were found to be completely within the normal range of healthy controls (17 to 38 fmol/mL; n = 50) and 52% were detected within the lower third or even below the normal range. In mild to moderate essential hypertension a diminished secretion of ANP may be responsible for an elevated blood pressure in these patients.     

Plasma atrial natriuretic factor in essential hypertension: relation to cardiac size, function and systemic hemodynamics

To evaluate determinants of elevated plasma atrial natriuretic factor levels in patients with hypertension, immunoreactive plasma atrial natriuretic factor in 54 normal subjects and 40 untreated hypertensive patients was compared with echocardiographic measurements of cardiac size, function and systemic hemodynamics. In normal subjects, plasma atrial natriuretic factor was related to age, systolic blood pressure and left atrial and ventricular chamber sizes, but only age and ventricular size were independent predictors. In untreated hypertensive patients, atrial natriuretic factor was directly related to age, atrial size, systolic pressure, peripheral resistance and ventricular systolic performance; age, atrial size and peripheral resistance were independent predictors. Eight patients with elevated atrial natriuretic factor values (greater than 25 fmol/ml) were significantly (p less than 0.01) older and had greater atrial and ventricular size and higher systolic pressure and function than normal subjects or patients with normal natriuretic factor levels. Plasma atrial natriuretic factor was inversely related to peak diastolic filling rate in normal subjects (r = -0.59; p less than 0.001), whereas it was positively related to the proportional contribution of atrial systole to left ventricular filling in hypertensive patients (r = 0.77; p less than 0.001). These findings suggest that in normal subjects, impairment of ventricular relaxation with age may contribute to atrial natriuretic factor secretion by increasing left atrial afterload; the correlation with left ventricular size may reflect physiologic fluctuations in plasma volume. In patients with uncomplicated hypertension, left atrial enlargement and consequent stronger atrial contraction contributed to increased atrial natriuretic factor release, whereas no independent relation existed with left ventricular hypertrophy or systolic function. Because ventricular relaxation was normal and ventricular size and systolic performance were increased in hypertensive patients with high atrial natriuretic factor levels, the observed increase in left atrial size and atrial contribution to ventricular filling might reflect a primary increase in venous return in this subset of hypertensive patients.     

Plasma atrial natriuretic peptide in essential hypertension after angiotensin converting enzyme inhibition

The authors have already found that the antihypertensive action of ₁-blockers is partially exerted through atrial natriuretic peptide (ANP). On the other hand, the antihypertensive action of angiotensin converting enzyme inhibitors (ACEI) seems to extend to other mechanisms. In this regard we studied the effect of the ACEI Cilazapril (C) on plasma ANP concentration in 21 patients, aged 40–64, with moderate degree essential hypertension. Assessments of the ANP and the other variables [(ECHO cardiac dimensions, blood pressure (BP)] were carried out before and after an 8-week treatment with 2–5 mg daily. ANP was purified by chromatography and assayed by radioimmunoassay (RIA). Systolic and diastolic BP decreased by 18% and 16%, respectively, left ventricular and left atrial diastolic diameters decreased by 6%. ANP increased by 5.7%. All changes were statistically significant. The discordant increase of ANP in relation to BP and cardiac dimensions suggests a direct effect of ACEI mediated either through the sympatholytic or the anti-carvoxypeptidase action. This effect may contribute to BP lowering.     

Plasma and urine concentrations of atrial natriuretic peptide in patients with diabetes mellitus

To examine whether plasma and urine concentrations of human atrial natriuretic peptide (hANP) are altered in patients with diabetes mellitus (DM), plasma and urine hANP concentrations were evaluated in 86 patients with diabetes mellitus using an extraction procedure. The mean recovery rate of extraction was 71.8 +/- 0.6% (mean +/- SEM). The major immunoreactive component of hANP in extracted plasma and urine appeared to be identical to synthetic alpha hANP as judged by reverse-phase high-performance liquid chromatography (HPLC). The patients were divided into three groups according to their renal complications. The patients in group 1 had no apparent abnormality in serum creatinine, serum or urine beta 2-microglobulin (beta 2-MG), or urine N-acetyl-beta-D-glucosaminidase (NAG); those in group 2 showed either beta 2-MG or NAG abnormality but no creatinine abnormality. The patients in group 3 were though to have an established diabetic nephropathy and showed a serum creatinine increase. Plasma ANP concentrations in groups 1, 2, and 3 were 10.7 +/- 2.1, 19.9 +/- 5.6, and 39.2 +/- 9.9 fmol/ml, respectively. These values in groups 2 and 3 were significantly higher than the control values (p less than 0.05 or p less than 0.01 versus 6.2 +/- 0.7 fmol/ml). Urine ANP concentrations in group 1 were also within normal range, though those in groups 2 and 3 markedly increased in comparison with normal values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma brain natriuretic peptide and atrial natriuretic peptide concentrations correlate with left ventricular end-diastolic pressure

The present study was designed to investigate whether brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) plasma concentrations correlate with left ventricular end-diastolic pressure (LVEDP), pulmonary capillary wedge pressure (PCWP), diastolic pulmonary arterial pressure (DPAP), right atrial pressure (RAP), or ejection fraction (EF). Plasma BNP and ANP levels were determined by commercial radioimmunoassays (Peninsula) after Sep Pak C₁₈ extraction in blood samples withdrawn from the pulmonary artery and the left ventricle or from the left ventricle and the femoral vein in 85 patients undergoing diagnostic cardiac catheterization. Linear and nonlinear regression analysis and the paired sample f-test were applied to the data. Pulmonary arterial plasma BNP and ANP levels showed a close nonlinear correlation with LVEDP (BNP: r=0.94, p < 0.001; ANP: r=0.81, p < 0.001), a significant linear correlation with PCWP, DPAP, and RAP, and a significant negative correlation with EE ANP concentrations decreased significantly from the pulmonary artery to the left ventricle and from the left ventricle to the femoral vein (p < 0.001). BNP levels also decreased significantly between the left ventricle and the femoral vein (p < 0.001), but there was no significant difference between pulmonary arterial and left ventricular BNP concentrations. BNP and ANP concentrations correlated significantly between pulmonary arterial and left ventricular blood samples (BNP: r = 0.99, ANP: r = 0.93, p < 0.001) and between left ventricular and peripheral blood samples (BNP: r=0.99, ANP: r=0.94, p<0.001). The present data suggest that peripheral plasma BNP and ANP levels are useful noninvasive indices of cardiac performance.     

Plasma concentration of human atrial natriuretic hormone in patients with connective tissue diseases

Summary Atrial natriuretic peptide (ANP), a peptide released from the cardiac atria, compensates blood volume expansion by its diuretic, natriuretic and vasoactive properties. We measured human plasma ANP(hANP) levels in patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and progressive systemic sclerosis (PSS) and found that their values were higher than those of healthy controls. In SLE patients, hANP levels correlated with serum creatinine concentration and the patients with proteinuria showed high levels of hANP. Administration of large amount of corticosteroid as a remission induction of the patients with SLE caused high levels of hANP. In patients with PSS, %FEV1 showed strong inverse correlations between hANP levels, and the patients with an enlarged second curvature of the heart had high levels of hANP. In patients with RA, no significant correlation was found between hANP levels and clinical variables including patients' age.     

Endogenous natriuretic factors: atrial natriuretic hormone and digitalis-like substance in Cushing's syndrome.

In order to investigate the effect of chronic hypercortisolaemia on endogenous natriuretic factors (atrial natriuretic hormone (ANH) and the Na+/K+ pump inhibitor) digitalis-like substance (DLS), and their relation to hypertension, 28 patients with pituitary- or adrenal-dependent Cushing's syndrome and six patients on high-dose prednisone treatment were studied. Plasma ANH levels were increased in patients with Cushing's syndrome (36.0 +/- 1.4 (S.E.M.) ng/l) compared with those in healthy controls (28.6 +/- 1.3 ng/l, P less than 0.01). In prednisone-treated patients, ANH levels (43.8 +/- 4.5 ng/l) were higher than those in patients with Cushing's syndrome and in controls (P less than 0.05 and P less than 0.01 respectively). DLS measured by radioimmunoassay and binding of [3H]ouabain to erythrocytes was not altered in patients with hypercortisolaemia. Slightly decreased DLS activity in the erythrocyte 86Rb uptake inhibition assay was found in patients with Cushing's syndrome (52.9 +/- 2.7%) compared with that in controls (60.9 +/- 1.8%, P less than 0.02). With the exception of cortisol (r = 0.52, P less than 0.01), none of the other factors determined correlated with the mean arterial pressure in patients with Cushing's syndrome. Thus, a chronic excess of endogenous and exogenous glucocorticoids increases plasma levels of ANH, but does not substantially influence DLS activity or plasma levels. Neither natriuretic factor is directly related to hypertension in Cushing's syndrome.     

Exaggerated natriuretic response to atrial natriuretic factor in rats developing spontaneous hypertension

The present study was designed to evaluate the renal response to atrial natriuretic factor (ANF) in young rats developing spontaneous hypertension (SHR) and compare this response to age-matched, normotensive controls (WKY) and adult animals. At 6 weeks of age, intravenous infusion of ANF (0.25 micrograms/kg min) in anesthetized, euvolemic rats produced a significantly larger natriuresis and diuresis in SHR compared with WKY rats; this strain difference was not observed in rats 11 weeks of age. SHR showed no age-related change in the natriuretic response to ANF, whereas adult WKY rats exhibited a greater response than young WKY rats. To determine the effect of renal perfusion pressure on the magnitude of the renal response to ANF, additional groups of 6- and 11-week-old SHR were studied while renal perfusion pressure was lowered acutely by aortic constriction (SHR-AC) to values similar to age-matched WKY rats. In young rats, the diuretic and natriuretic response to ANF was greatest in SHR, intermediate in SHR-AC, and lowest in WKY rats. In adult animals, the natriuretic and diuretic response was similar in SHR and WKY rats and tended to be less in SHR-AC. These results in both 6- and 11-week-old SHR are consistent with previous reports that the magnitude of the response to ANF is directly related to acute changes in renal perfusion pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

The atrial natriuretic factor in hypertension

Plasma immunoreactive atrial natriuretic factor (IR-ANF) concentration measured by radioimmunoassay after extraction on Sep-Pak cartridges was studied in 64 control normotensive subjects, 25 patients with labile essential hypertension, 67 patients with mild essential hypertension (diastolic pressure between 90 and 105 mm Hg and no left ventricular hypertrophy) and 9 patients with moderate to severe essential hypertension (diastolic pressures between 105 and 120 mm Hg). An additional group of 16 patients under medication but without effective control of their blood pressure and with diastolic pressure above 110 mm Hg also was studied. Results show that plasma IR-ANF concentrations are within normal range in patients with labile, mild, and moderate hypertension. In view of the reported increased right and left atrial pressures and distension in patients with mild and moderate hypertension, these findings strongly suggest a state of hyporesponsiveness of the atria to release ANF.     

Plasma atrial natriuretic polypeptide concentrations during and after reversion of paroxysmal supraventricular tachycardias

Plasma concentrations of immunoreactive atrial natriuretic polypeptide were raised in 22 of 23 patients with paroxysmal supraventricular tachycardia and in all seven patients with atrial flutter. Plasma concentrations of atrial natriuretic polypeptide rose soon after the onset of supraventricular tachycardia. A sample taken 30 minutes after reversion to sinus rhythm (pharmacological or non-pharmacological) showed a significant fall in 19 of the 23 patients with paroxysmal supraventricular tachycardia and all seven patients with atrial flutter. Because atrial natriuretic polypeptide has powerful natriuretic and diuretic properties, an increase may contribute considerably to the polyuria that is often associated with episodes of supraventricular tachycardia.