Atrial natriuretic factor in human blood.

To determine whether atrial natriuretic factor (ANF) is a circulating hormone in men, a radioimmunoassay suitable for the estimation of ANF in human plasma was developed and the nature of plasma ANF was characterized. Plasma ANF was extracted before radioimmunoassay by affinity chromatography on a column of ANF antibody-coupled agarose. When plasma ANF extract was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, with the radioimmunoassay of the eluted gel slices for ANF, almost all of the ANF activities ran in the 3,000-mol-wt area, while three peaks of ANF were observed in human atrial tissue extract, molecular weights of which corresponded to 14,000, 6,000, and 3,000, respectively. Reversed-phase high performance liquid chromatography of atrial tissue extract resolved multiple forms of ANF. In contrast, one major peak was observed in human plasma extract, and its retention time coincided with that of synthetic human alpha-atrial natriuretic polypeptide. When 500 ml of 0.9% saline was infused into six healthy subjects over 45 min, plasma levels of ANF were unequivocally elevated. The mean plasma ANF concentrations rose from the baseline (23.0 +/- 2.5 pg/ml, mean +/- SEM, n = 6) to the peak (41.8 +/- 4.9 pg/ml, mean +/- SEM) at 75 min postinfusion. No significant change in plasma ANF, on the other hand, was found in the control group. These results suggest that ANF is a circulating hormone in men and is secreted in response to isotonic volume expansion.     

Atrial natriuretic factor after cardiac surgery with cardiopulmonary bypass in children.

OBJECTIVE: To determine circulating atrial natriuretic factor (ANF) concentrations in the postoperative state and to define potential hemodynamic determinants of regional plasma ANF concentrations. DESIGN: Cohort study. SETTING: Pediatric ICU in a university hospital. PATIENTS: Twenty-two children, mean age 4.2 yrs (range 0.9 to 13.5), were studied 18 hrs after corrective surgery on cardiopulmonary bypass. The underlying cardiac malformations were ventricular septum defect (n = 5), transposition of great arteries (n = 5), tetralogy of Fallot (n = 4), pulmonary stenosis (n = 3), and miscellaneous (n = 5). INTERVENTIONS: In addition to the commonly monitored variables in postoperative cardiac patients, blood volume was estimated by the 125I albumin method, and plasma samples for radioimmunoassay determination of ANF concentrations were taken simultaneously from indwelling catheters. MEASUREMENTS AND MAIN RESULTS: Compared with normal age-matched values, plasma ANF concentrations were increased in all patients, with values tending to be highest in the left atrium, followed by systemic artery, superior vena cava, and pulmonary artery (345 +/- 158, 333 +/- 169, 311 +/- 154, and 272 +/- 160 pg/mL, respectively [mean +/- SD; NS]). Simple regression analysis demonstrated a moderate correlation between blood volume and the concentration of ANF in the superior vena cava (p less than .05). Stepwise multivariate analysis showed no significant independent predictor of plasma ANF concentrations. CONCLUSIONS: Plasma ANF concentrations are increased after open-heart surgery in children, with moderate direct correlation to blood volume. The wide scatter of increased hormone concentrations may be explained by the many factors known to influence circulating ANF concentrations, such as age, underlying disease, cardiovascular state, and drugs.     

Atrial natriuretic factor increases after a protein meal in man

1. The renal function changes induced by dietary protein are thought to result from the activity of hormonal factors that remain as yet undefined. Since a meat meal and high dose atrial natriuretic factor (ANF) infusions have similar effects on glomerular filtration rate, natriuresis and kaliuresis, we decided to investigate the possibility that a protein meal could stimulate ANF activity. 2. We studied 10 normal volunteers who had a fixed protein and sodium intake for 7 days before the experiments. The subjects received a meat meal (1-1.5 g of protein/kg) and, on a separate occasion, a carbohydrate meal that had a similar caloric, sodium and potassium content. Diuresis was stimulated with water ingestion, and urine collections were obtained before the meals (baseline) and after the meals for a period of 3 h. Blood samples were obtained 30 min and 5 min before the meals and every hour for 3 h in the period after the meal. 3. The protein meal, but not the carbohydrate meal, was associated with parallel increments in plasma immunoreactive ANF (i-ANF), natriuresis, kaliuresis and glomerular filtration rate (estimated from creatinine clearances) which reached peak values 2-3 h after the meal. The mean increment of plasma i-ANF after the protein meal represented a twofold increase over baseline levels. 4. We conclude that ANF may participate in the physiological response to an oral protein load.     

What stimulates atrial natriuretic factor release during exercise?

Prior studies have shown that circulating atrial natriuretic factor (ANF) increases during short-term exercise, but the mechanism controlling ANF release, as well as the effect of exercise training on ANF release, remains unclear. Fifteen healthy mongrel dogs underwent short-term exercise testing before and after a 12-week period of exercise training (n = 8) or cage confinement (n = 7). ANF, norepinephrine, epinephrine, right atrial pressure, and heart rate were measured simultaneously at rest and during exercise at the time of each acute exercise study. Data were analyzed for all animals with normal baseline ANF values. Exercise training had no modulating effect on circulating ANF levels at rest or during exercise. Therefore, data before and after exercise training or cage confinement were grouped (n = 24) to determine the effects of short-term exercise. ANF levels increased from 49 +/- 2 pg/ml at rest to 60 +/- 4 pg/ml during exercise (p less than 0.05). Heart rate, norepinephrine, and epinephrine values also increased, but right atrial pressure actually decreased from 2.3 +/- 0.9 mm Hg at rest to -3.8 +/- 0.9 mm Hg during exercise (p less than 0.05). There was no correlation between ANF concentrations and levels of these other variables either at rest of during exercise. By demonstrating an increase in ANF with a simultaneous decrease in right atrial pressure, this study clearly shows that increased right atrial pressure is not the secretory stimulus for ANF release during exercise in the normal dog. The lack of correlation between ANF and right atrial pressure, heart rate, norepinephrine, and epinephrine levels suggests that factors other than these variables stimulate ANF release during short-term exercise.     

Atrial natriuretic peptide: physiological release associated with natriuresis during water immersion in man

Thermoneutral water immersion produces a physiological increase of thoracic blood volume, raises central venous pressure and increases urinary sodium excretion by a hitherto ill-understood mechanism. We have investigated whether this enhanced sodium excretion could be mediated by the recently discovered natriuretic factor, atrial natriuretic peptide (ANP). During water immersion there was a highly significant (P less than 0.001) twofold increase of the mean plasma ANP concentration and a doubling of the mean urinary sodium excretion. Both were unchanged during the control experiments. These results are consistent with the hypotheses that ANP is released into plasma in response to central blood volume expansion and that it functions as a natriuretic hormone in normal man under physiological conditions.     

Atrial natriuretic factor during exercise in male endurance athletes: effect of training

Summary. Nine male endurance runners were evaluated with bicycle exercise testing before a training break of 3 weeks duration, and 0, 2 and 4 weeks after resumption of training to assess the effects of training on resting and exercise plasma atrial natriuretic factor (ANF) measured at 50% and 100% of predetermined maximal workload. Maximal oxygen uptake and lean body mass (LBM) were calculated at each time point. Maximal oxygen uptake decreased during training break, but rose 4 weeks after resumption of training (P<0·01). LBM was unchanged after inactivity, but rose after resumption of training (P<0·01). Plasma ANF at rest did not change throughout the experiment. ANF levels rose after training break at maximal workload (P<0·05), and decreased 4 weeks after resumption of training, but only at submaximal workload (P<0·05). No correlations between systolic blood pressure, mean blood pressure or heart rate and ANF could be demonstrated. These results indicate that the haemodynamic changes associated with endurance training are reflected in plasma ANF levels during exercise, but not at rest. The full adaptation of ANF release to training probably requires more time than the 4 weeks reported for the haemodynamic adjustments.     

Atrial natriuretic factor in normothermic and hypothermic cardiopulmonary bypass

BACKGROUND: To evaluate the plasmatic changes of atrial natriuretic factor (ANF) during and after cardiopulmonary bypass (CPB) in normothermia and hypothermia. METHODS: Twenty-three patients (n = 23) undergoing coronary artery bypass graft surgery were randomly assigned to two groups. In Group I (n = 11), the patients underwent operation in normothermia; in Group II (n = 12), the operation was performed in hypothermia (26 degrees C). RESULTS: Plasma ANF levels were determined after induction of anaesthesia, at the end of CPB and one hour postoperatively. There were no demographic differences between the two groups, diuresis (p = 0.90) and natriuresis (p = 0.95). Plasma levels of ANF were significantly elevated during and after CPB in both groups (p < 0.01). The groups differed significantly for plasma levels of ANF during CPB and postoperatively (p < 0.05), but did not differ prebypass (p = 0.08). There was no correlation in either group between ANF release and central venous pressure, natriuresis and diuresis. There was only a borderline relationship between ANF concentration and diuresis after CPB in Group I. CONCLUSION: CPB triggers the production and release of ANF. The present study demonstrates a significantly enhanced ANF release during hypothermia and reperfusion after ischaemia. Thus, these data suggest the protective role of ANF on the hypoxic myocardium, and they confirm that ANF does not play a role in diuresis and natriuresis during and after hypothermic CPB.     

Atrial natriuretic factor in cats subjected to acute myocardial ischaemia.

Eighteen anaesthetized open chest cats were subjected to 10, 30, or 50 min occlusion of the left anterior descending coronary artery (LAD). Heart rate, left ventricular end-diastolic (LVEDP) and systolic pressure (LVSP), and dp/dt were continuously recorded during the experiments. Prior to LAD-occlusion, and just before termination of the experiments, blood samples were collected from the left femoral artery for measurements of atrial natriuretic factor (ANF), catecholamines, electrolytes, urea, and creatinine. Simultaneously, biopsies were collected from the right auricular wall. The tissue was embedded in Lowicryl K4M, and ultrathin sections were incubated with anti-ANF antibodies and secondary antibodies conjugated to gold particles. The density of ANF-containing atrial-specific granules labelled with gold particles was morphometrically calculated. LVEDP increased significantly in all three time groups, and when pooling the pre- and postocclusion values, there was an increase from 5.1 +/- 0.4 to 10.3 +/- 1.2 mmHg (p < 0.05). The noradrenaline level increased from 0.93 +/- 0.18 to 2.34 +/- 0.75 nmol l-1 (p < 0.05) after LAD-occlusion. Similarly, the mean plasma level of ANF in the 18 cats increased from 57.6 +/- 11.9 to 98.9 +/- 22.6 pmol l-1 (p < 0.05). Atrial granular density appeared to decline after 10 min of occlusion (from 0.141 +/- 0.017 to 0.127 +/- 0.022 granules-1 microns 2 sarcoplasm), and after 30 min there was a significant decrease (0.080 +/- 0.012 granules/microns 2, p < 0.05). However, after 50 min occlusion the granular density was almost restored (0.133 +/- 0.017 granules/microns 2). Plasma ANF showed a positive linear correlation to LVEDP and to the noradrenaline level.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atrial natriuretic factor in chronic heart failure]

Seventy-six patients with chronic heart failure, stages I-III, that developed after different heart diseases were examined. Catheterization of the right heart was carried out in 51 patients. The concentration of immunoreactive atrial natriuretic factor (ANF) in peripheral blood plasma and in the blood from the right atrium was increased in patients and rose as heart failure progressed. No correlation was discovered between the character of heart disease and the concentration of immunoreactive ANF in the plasma. The latter one was directly dependent on the wedging pressure in the pulmonary artery and on the pressure in the right atrium. The level of immunoreactive ANF in the atrium was higher than in the periphery. However, that was not of statistical power.     

Atrial natriuretic peptide: physiological release associated with natriuresis during negative pressure breathing in man

1. Negative pressure breathing was one of the first physiological tools used to study the renal effects of redistribution of the blood volume from the peripheries to the thorax. The recent discovery of a putative natriuretic hormone (atrial natriuretic peptide, ANP) in cardiac atrial tissue has rekindled interest in the effect of the cardiovascular system on renal function. We have therefore studied the effects of this physiological manoeuvre on plasma ANP concentrations and renal responses. 2. Plasma concentrations of ANP, plasma renin activity and plasma aldosterone concentration were measured during an 80 min period of negative pressure breathing at -12 cmH2O pressure in six hydrated normal subjects. Identical control studies were performed in the same subjects at at least 1 week apart. 3. Negative pressure breathing resulted in a natriuresis and diuresis which were associated with a significant rise in plasma ANP concentration. The natriuresis occurred despite an increase in plasma renin activity and in plasma aldosterone concentration. 4. These findings, under specific carefully controlled conditions, support the previously contentious postulate that negative pressure breathing enhances sodium excretion, in addition to its well-recognized diuretic effect. They add further weight to the hypothesis that expansion of the central blood volume is an important stimulus to the release of ANP from the heart (acting by way of atrial distension), and suggest that changes of plasma ANP concentration may have induced the natriuresis which occurred in the face of a modest activation of the sodium-retaining renin-aldosterone system.     

Atrial natriuretic peptide inhibits osmolality-induced arginine vasopressin release in man

1. Eight normal volunteers were infused with 5% saline (5 g of NaCl/100 ml) at a rate of 0.06 ml min-1 kg-1 for 120 min to increase plasma osmolality and plasma arginine vasopressin. Human atrial natriuretic peptide (alpha-hANP; 100 micrograms) or placebo was given in random order in a double-blind cross-over design for the last 20 min of the saline infusion. 2. Compared with the placebo infusion, atrial natriuretic peptide (ANP) produced a 43% greater sodium excretion and a 34% greater urinary volume in the subsequent hour. 3. Mean plasma immunoreactive ANP did not increase in response to changes in osmolality and rose to a peak of 118 pg/ml during the alpha-hANP infusion. alpha-hANP produced significant suppression of mean plasma arginine vasopressin over the 60 min after the infusions. 4. We conclude that ANP is not released in response to increased osmolality in vivo, and that it inhibits osmolality-induced arginine vasopressin release in man.     

Atrial natriuretic factor, the kidney and high blood pressure

The discovery of atrial natriuretic factor (ANF) constitutes a major advance in our knowledge of negative cell regulatory pathways leading to vasodilation. The biochemical mechanisms of the action of ANF at the cellular level appear to be mediated by the cGMP- particulate guanylate cyclase system. In the kidney, the main cGMP increasing effect of ANF occurs at the level of the glomeruli, but it appears that action of ANF at the lowest part of the distal tubule is required for its natriuretic activity. Although most current knowledge concerning ANF has been obtained with pharmacological doses of the hormone, it appears that endogenous manipulations of ANF, such as those occurring with postural change, are associated with physiological consequences including increases of cGMP, natriuresis, and diuresis. In both experimental and human hypertension, increased plasma levels of ANF are secondary to higher blood pressure. In hypertension, the administration of ANF leads to an exaggerated renal response. We propose as a hypothesis that an abnormality in the expression of a vasodilatory system, such as ANF-cGMP, may play a role in the pathogenesis of hypertension.     

Atrial natriuretic factor in the pediatric intensive care unit

ANF is a newly discovered peptide hormone that has significant implications for critical care physicians. This hormone, released from the heart, is especially responsive to fluid challenges as well as to many of the drugs commonly used in the ICU, including pressor and anesthetic agents. It has potent arterial vasodilating effects in pharmacologic doses and may be an important natural vasodilating agent, especially in the renal vascular bed. In patients on dopamine, it may potentiate the renal vasodilating effect and may provide an effective therapy for developing acute renal failure. Children with congenital heart disease and patients with CHF have elevated levels that clearly alter the aldosterone-angiotensin II system and may help us to understand and treat these conditions more effectively. Additionally, ANF may be a marker for adequacy of treatment in these disease states. The potential uses for ANF include diuresis in patients with fluid overload and diuretic resistance, treatment of CHF, and as a short-acting vasodilator. In the ICU, many therapies affect cardiac pressures and volume regulation. Positive-pressure ventilation may decrease the release of ANF by decreasing venous return and thus contribute to water retention. Drugs used in the ICU may directly affect ANF levels and markedly affect the homeostasis of fluid and electrolyte balance. This hormone system interacts intimately with renin, angiotensin II, and aldosterone. These interactions may play a significant role in the development of essential hypertension. Although not addressed in this article, the treatment and understanding of essential hypertension may be significantly advanced by understanding these relationships. It is clear that ANF acts as a hormone with complex interactions between the heart, volume status, electrolyte balance, renin-angiotensin II-aldosterone, vasopressin, and vascular tone. Although currently no definitive picture exists for these complex interactions, this is an exciting new hormone with significant implications for patient management in the ICU. As research continues, the picture will become clearer and our understanding of this new hormone more precise.     

Atrial natriuretic peptide and related peptides.

In recent years, biomarkers have been recognized as important tools for diagnosis, risk stratification, and therapeutic decision-making in cardiovascular diseases. Currently, the clinical potential of several natriuretic peptides is under scientific investigation. The well-known counter-regulatory hormones are atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), dendroaspis natriuretic peptide (DNP) and urodilatin, which play an important role in the homeostasis of body fluid volume. ANP and BNP have already been demonstrated to have diagnostic usefulness in a great number of studies, which have progressed from bench to bedside. This article summarizes existing data on ANP and related peptides in cardiovascular and other disorders, and outlines the potential clinical usefulness of these markers.     

Atrial natriuretic factor: sodium transport in human erythrocytes

The effect of partially purified rate atrial natriuretic factor on sodium efflux from sodium-loaded human erythrocytes was studied. High molecular weight (10 000-30 000) and low molecular weight (3000-10 000) fractions of atrial extract were prepared by gel filtration; they had natriuretic activity in rats. Neither fraction affected sodium efflux in erythrocytes. The results suggest that atrial natriuretic factor acts in the kidney by mechanisms other than through inhibition of the Na+-K+ exchange pump or the Na+-K+ cotransport system.