Atrial Natriuretic Factor Concentrations Research Articles

Diminished release of atrial natriuretic factor in calves with a total artificial heart.

Venous hypertension after total artificial heart (TAH) replacement, a common problem in humans as well as experimental animals, is thought to be related to reduced release of atrial natriuretic factor (ANF) due to atrial damage. To verify this hypothesis, we stimulated the release of ANF in 6 calves before (-7 days) and after TAH replacement (+25, +50, +80, and +100 days) by the rapid (+ = 10 min) infusion of 2 L of Ringer's solution. In normal calves (-7 days) this procedure induced a rise in plasma concentration of ANF from 18.5 +/- 12 to 31.6 +/- 12 pmol/L (p < 0.05). After TAH the ANF release continuously decreased (analysis of variance, p < 0.02). Thus, ANF increased by 9.8 +/- 9.3, 6.8 +/- 17.5, 0.4 +/- 5.2, and 0.5 +/- 3.2 pmol/L at days 25, 50, 80, and 100, respectively. The central venous pressure increased by 3.4 +/- 1.5 mm Hg (before TAH) and by 6 +/- 2.9 mm Hg (after TAH) during this procedure. A decrease in plasma concentrations of aldosterone, most likely due to extracellular volume expansion and a decrease in total protein plasma concentrations and in hematocrit due to the dilution of blood, was seen in each experiment. Necropsy demonstrated massive atrial dilatation and myocardial dystrophy with atrial fibrosis. ANF granules were present to a small extent in every calf. We conclude that rapid intravenous infusion is an adequate stimulus to release ANF in normal calves. After TAH implantation the release of ANF by high venous pressure declines although ANF granules are still present in the damaged atrial stumps. Therefore, the loss of stimulated ANF could contribute to the observed increase in venous pressure in TAH calves although other pathophysiologic mechanisms cannot be excluded.

Atrial natriuretic factor concentrations during pregnancy and in the postpartum period.

Atrial natriuretic factor (ANF) is a hormone that regulates fluid and electrolyte homeostasis. Increased intra-atrial pressure or atrial distention, which might occur secondary to intravascular volume expansion, stimulate the secretion of ANF by human atrial myocytes. During normal human pregnancy, there is a progressive increase in total intravascular fluid volume. Thus, we asked the following question: Does this physiologic adaptation to pregnancy result in an increase in ANF concentrations? Concentrations of alpha-human ANF (alpha-hANF) were measured by a specific radioimmunoassay in venous blood samples obtained longitudinally in the first, second, and third trimesters of pregnancy, during the intrapartum period, in the early postpartum period, and 6 to 8 weeks postpartum from 11 normal women who had no antepartum, intrapartum, or postpartum complications. Maternal circulating alpha-hANF levels were not different from those seen in the nonpregnant state. However, higher alpha-hANF concentrations were noted in the early postpartum period. Although the hypervolemia of normal pregnancy is not associated with higher alpha-hANF concentrations, other possibilities (such as increased ANF clearance, dilutional effects) need to be investigated. Finally, the etiology for the transient increase in alpha-hANF levels in the early postpartum period remains to be elucidated.

Circulating endothelin in acute ischaemic syndromes.

Endothelin is an extremely potent vasoconstrictor that may have a role in the pathogenesis of acute myocardial ischaemia. Atrial natriuretic factor is an endogenous antagonist of endothelin. To find the pattern and possible importance of circulating endothelin in ischaemic heart disease, concentrations in normal controls and those in patients with stable and unstable angina, acute myocardial infarction, and chronic cardiac failure were compared. The relation between circulating concentrations of endothelin and atrial natriuretic factor in the aftermath of myocardial infarction was also examined. Eighteen patients with acute myocardial infarction, 10 with unstable angina, 10 with stable angina, 12 with chronic cardiac failure, and 10 normal controls were studied. Endothelin concentration was measured in venous plasma by radioimmunoassay. In patients with acute myocardial infarction simultaneous concentrations of endothelin and atrial natriuretic factor were measured on admission and at one, four, and 24 hours. Mean concentrations (SEM) of endothelin were 5.72 (0.19) fmol/ml in controls, 6.56 (0.48) fmol/ml in stable angina, 6.41 (0.48) fmol/ml in unstable angina, and 13.83 (0.95) fmol/ml in chronic cardiac failure. In acute myocardial infarction concentrations were 8.81 (0.69) fmol/ml on admission, 11.85 (1.02) fmol/ml at one hour, 11.88 (1.10) fmol/ml at four hours, and 7.30 (0.49) fmol/ml at 24 hours. Concentrations of atrial natriuretic factor at the same times were 68.1 (13.1) pg/ml, 8.4 (1.5) pg/ml, 24.4 (4.1) pg/ml, and 42.0 (6.9) pg/ml. Plasma endothelin is raised in chronic heart failure and in the aftermath of acute myocardial infarction but not in stable or unstable angina. After myocardial infarction endothelin concentrations are raised whereas concentrations of atrial natriuretic factor are relatively low. The role of endothelin in the pathogenesis of acute myocardial infarction and its interactions with other humoral factors require further investigation.

Effect of changes in sodium intake on atrial natriuretic factor (ANF) and peptides derived from the N terminus of the ANF prohormone in the rat.

The purpose of the present study was to determine whether variations in salt intake would alter the plasma concentrations of atrial natriuretic factor and the N-terminal atrial natriuretic factor prohormone peptides proANF 1-98 and proANF 31-67. Two groups of rats were placed on different salt intakes for 1 week. The low salt group of rats was fed a diet providing less than 0.1 mM NaCl/day and given deionized water to drink. The normal salt group of rats was fed regular rat chow with deionized water to drink, providing them with approximately 2 mM NaCl/day. Plasma atrial natriuretic factor was 204 +/- 60 pg/ml (mean +/- SE) in normal salt rats and was significantly lower in the low salt group (44 +/- 13 pg/ml, P less than 0.01). ProANF 1-98 was also significantly higher in the normal salt group (635 +/- 47 pg/ml) compared with the low salt group (353 +/- 33 pg/ml, P less than 0.01). ProANF 31-67 was 123 +/- 21 pg/ml in the normal salt group and 59 +/- 12 pg/ml in the low salt group (P less than 0.05). Plasma renin activity in ng angiotensin l/ml/hr averaged 1.80 +/- 0.15 in the normal salt group of rats and was significantly higher in the low salt group of rats (5.66 +/- 1.07, P less than 0.05). These results suggest that atrial natriuretic factor and the atrial natriuretic factor prohormones may play a role in the physiological adjustments to low salt intake.

Atrial natriuretic factor in essential hypertension: echocardiographic and humoral correlates.

Aim of this study was to assess the relationship between plasma concentration of atrial natriuretic factor (ANF) and its two-dimensional echocardiographic (left ventricular mass, left atrium diameter) and humoral (plasma renin and aldosterone) variables in essential hypertension (EH). We evaluated 32 patients with uncomplicated mild to moderate EH and 10 controls. They were studied in the supine position after 7 days of constant dietary sodium intake and were off therapy since at least 3 weeks. ANF values overlapped between EH patients and controls (27.8 +/- 11.5 vs. 19.5 +/- 7.4 pg/ml, p = NS). In EH, no significant correlation was found between ANF values and left ventricular mass (r = 0.29), left atrial diameter (r = 0.04), mean arterial blood pressure (r = 0.26), plasma renin activity (r = 0.00), and aldosterone (r = 0.26). In EH, ANF values overlapped between the 15 patients with hypertrophy and the 17 patients with normal ventricular mass: 30.3 +/- 17 vs. 25.6 +/- 10.6 pg/ms (p = NS). We conclude that there is a substantial overlap in plasma ANF values between mild to moderate uncomplicated EH and controls, and left ventricular hypertrophy is not a major independent stimulus to ANF release in EH.

PLASMA ATRIAL NATRIURETIC FACTOR DURING ETHANOL INGESTION IN VOLUME-LOADED SUBJECTS

The present study was designed to test whether ethanol ingestion affects plasma atrial natriuretic factor (ANF) concentration in healthy volunteers. On the basis of previous studies showing that ethanol induces a diuretic response and a decrease in atrial size (atrial distension), it was hypothesized that ethanol intake might be associated with a decrease in plasma ANF level. To somewhat increase plasma ANF level, the subjects were slightly loaded with water before the trial. As compared with juice, ethanol, 1 g/kg within 1 hr, increased urine output [405 +/- 37 (mean +/- SEM) ml/hr vs. 197 +/- 20 ml/hr, P less than 0.001]. Left atrial size decreased similarly (P less than 0.001) with both drinks. Plasma ANF concentration did not change with either ethanol or juice during the 3-hr study period. No changes were observed in plasma arginine vasopressin concentration and plasma renin activity. Our results are in conflict with previous reports in fasted subjects showing significant changes in plasma concentrations of the same hormones. Thus, the basal fluid balance seems to be crucial to the hormonal response to ethanol. The plasma concentrations of the hormones measured in this study do not directly explain the diuretic response to ethanol observed in slightly volume-loaded subjects.

Acute Inhibition of Endopeptidase 24.11 in Essential Hypertension

The acute renal, endocrine, and hemodynamic effects of the orally active endopeptidase inhibitor SCH 34826 (400 mg every 6 hours for five doses) were investigated in a group of 6 male patients [with established mild to moderate essential hypertension and left ventricular (LV) hypertrophy] in a balanced random-order double-blind, placebo-controlled cross-over study. Plasma atrial natriuretic factor (ANF) concentrations increased (p < 0.05) to fourfold control values after the first dose of inhibitor, but later postdose increments of ANF were less pronounced. Plasma cyclic GMP also increased significantly (p < 0.05). These effects were associated with a transient modest but significant (p < 0.05) increase in sodium excretion (50 mmol sodium in excess of placebo values) that was complete in 24 h. Mean 24-h urinary excretions of cyclic GMP and immunoreactive ANF were also significantly increased by 55 and 86%, respectively. Other urine indexes (including other electrolytes, volume, creatinine, aldosterone, and cortisol) and renal hemodynamics [including glomerular filtration rate (GFR) and effective renal plasma flow (RPF)] were unchanged. Renin-angiotensin-aldosterone system (RAAS) activity was not significantly altered. Plasma epinephrine increased after the initial three doses of SCH 34826. Systolic blood pressure (SBP) and heart rate (HR) were not altered by SCH 34826. Diastolic BP (DBP) increased slightly (p = 0.044). Acute inhibition of endopeptidase 24.11 by SCH 34826 in essential hypertension caused significant increments in plasma ANF and cyclic GMP together with modest natriuresis. No antihypertensive effect was observed in the first 30 h of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma renin activity in alcoholic liver disease

purpose and patients and methods: The relationship of plasma renin activity (PRA) to indices of circulatory filling and other possible determinants of renin secretion was studied in 31 men with alcoholic liver disease. Characteristics of patients with normal and increased PRA values were examined. Significant differences guided subsequent simple and multiple regression analysis. results: Supine PRA was increased (greater than 2.4 ng/mL/h on a 200 mEq/d intake of sodium, ranging as high as 33 ng/mL/h) in 14 of 57 studies. Nonascitic patients with elevated PRA values were significantly younger than those with normal PRA values. Among patients without ascites, the plasma atrial natriuretic factor concentration correlated inversely with PRA. Ascitic patients with elevated PRA values had a significantly reduced serum sodium concentration, urinary sodium excretion, creatinine clearance, and arterial pressure. Systemic vascular resistance, plasma norepinephrine and caffeine concentrations, and left atrial volume were similar in patients with and without increased PRA values. Univariate followed by multiple regression analysis identified age and plasma atrial natriuretic factor concentration as significant independent correlates of PRA in patients without ascites ( R 2 = 0.54). Serum sodium concentration and urinary sodium excretion were significant correlates of PRA in patients with ascites ( R 2 = 0.80). conclusion: The associations of PRA in alcoholic liver disease are diverse and potentially complex. Age and plasma atrial natriuretic factor concentration are important in patients without ascites. In patients with ascites, tubular delivery of sodium to the macula densa, as modified by the filtered load and proximal reabsorption, appeared to be a principal association of PRA. Indices of circulatory filling did not emerge as clearly independent associations of PRA. Increased PRA values in patients with ascites may be an effect of sodium retention rather than part of its cause.

Regulation of proximal tubule function by angiotensin.

1. Independent of its effects on renal haemodynamics and glomerular filtration, angiotensin II (AII) has direct actions on the proximal tubule involving transepithelial Na+, H+, HCO3-, and water reabsorption, ammoniagenesis, gluconeogenesis and renal growth. 2. The effects of AII on water and electrolyte transport are biphasic and dose-dependent, such that low concentrations (10(-12)-10(-9) mol/L) stimulate reabsorption whereas high concentrations (10(-7)-10(-6) mol/L) inhibit reabsorption. Similar dose-response relations have been obtained for luminal and peritubular addition of AII. 3. The cellular responses to AII are mediated via an AT-1 receptor coupled via G-regulatory proteins to several parallel signal transduction pathways. Low doses inhibit the basolateral adenylate cyclase, lower intracellular cAMP and withdraw the inhibitory effect of protein kinase A on the luminal Na/H exchanger. Stimulation of this exchanger may also occur due to AII-receptor activation of phospholipase C to release diacyl glycerol, or by local transduction in the brush-border membrane involving phospholipase A2. 4. Inhibition of proximal fluid reabsorption is associated with increased intracellular Ca2+ released from intracellular stores, or entering via voltage-sensitive channels in response to the release of inositol-1,4,5-trisphosphate, or following Ca2+ channel opening induced by the arachidonic acid metabolite 5,6-epoxy-eicosatrienoic acid. 5. The stimulatory actions of peritubular AII on proximal transport are inhibited by physiological concentrations of atrial natriuretic factor (ANF) and by parathyroid hormone (PTH). 6. It is concluded that intrarenal AII acts to maintain optimal matching of fluid reabsorption and filtered load in response to changes in sodium balance, as well as to promote acidification of the urine during acidosis and perhaps to potentiate tubular growth following renal injury.

Baroreflex and Atrial Natriuretic Factor Concentration Correlate with Myocardial Infarct Size and Predict Early Death in Rabbits

Baroreflex and Atrial Natriuretic Factor Concentration Correlate with Myocardial Infarct Size and Predict Early Death in Rabbits

Transient myocardial ischemia stimulates atrial natriuretic factor release

Atrial natriuretic factor release during transient myocardial ischemia was investigated in 29 patients with coronary artery disease and symptoms of angina (Canadian Cardiovascular Association classes II–III). Eleven patients (group I) underwent single-vessel percutaneous transluminal coronary angioplasty. Repeat determinations of mean pulmonary artery wedge pressure and blood sampling from pulmonary artery for atrial natriuretic factor measurements were performed at baseline, and at 2, 5, and 15 minutes after percutaneous transluminal coronary angioplasty was begun. Baseline atrial natriuretic factor levels (34.6 ± 4.5 pg/ml) rose to 56.3 ± 7.3 pg/ml ( p = 0.02) and decreased at 5 minutes (43.7 ± 5.7 pg/ml, not significant) and 15 minutes (35.3 ± 4.4 pg/ml, not significant). Changes in atrial natriuretic factor concentrations were significantly correlated with those in mean pulmonary artery wedge pressure (2 minutes: r = 0.69, p = 0.02; 5 minutes: r = 0.90, p < 0.001). In group II ( n = 10) the increase in atrial natriuretic factor after dye load occurred later (baseline: 25.8 ± 2.1; 60 minutes: 40.6 ± 2.6 pg/ml; p = 0.005) than that observed in group I after percutaneous transluminal coronary angioplasty. In group III, atrial natriuretic factor during angina rose as early (baseline 11.3 ± 1.3; 5 minutes: 20 ± 2.3 pg/ml; p = 0.006) as after percutaneous transluminal coronary angioplasty. Results indicate that transient myocardial ischemia stimulates atrial natriuretic factor release, probably through changes in cardiac function.

Pulmonary extraction and left atrial secretion of atrial natriuretic factor during cardiopulmonary bypass surgery

We have investigated the role of the lungs in the extraction of atrial natriuretic factor (ANF) by measuring plasma levels in samples taken from the central circulation in 12 patients (mean age 59 years; range 43 to 68) undergoing cardiac surgery. We also investigated the effects of cardiopulmonary bypass on ANF levels. ANF levels (mean ± SD) were lower in puimonary venous samples (41 ± 20 pg/ml) than in pulmonary arterial samples (54 ± 18 pg/ml; p < 0.001), demonstrating 24% extraction of ANF by the lungs. Both left atrial (47 ± 23 pg/ml) and systemic arterial levels (52 ± 22 pg/ml) were higher than pulmonary venous levels (both p < 0.05), indicating secretion of ANF into the left side of the heart. During cardiopulmonary bypass, plasma ANF concentration fell from 68 ± 23 pg/ml before aortic cross-clamping to 35 ± 13 pg/ml 10 minutes after and 28 ± 9 40 minutes after the application of clamps (both p < 0.001). A rebound rise to 122 ± 33 pg/ml followed the release of the clamp ( p < 0.001). This study demonstrates that ANF is extracted by the lungs and secreted directly into the left side of the heart. The considerable fall in plasma levels that was observed during aortic cross-clamping might contribute to the neurohumoral activation and increased peripheral resistance observed after prolonged cardiopulmonary bypass and to the risk of renal ischemic injury.

Enhanced release of atrial natriuretic factor during exercise-induced myocardial ischaemia in patients after acute myocardial infarction

To determine whether acute myocardial ischaemia induced by dynamic exercise can lead to changes in plasma levels of atrial natriuretic factor, we performed symptom-limited bicycle electrocardiographic tests in 20 males with recent acute myocardial infarction and in 8 control males. Ten patients developed exercise-induced myocardial ischaemia and 10 patients did not. There were no significant differences between the two groups with regard to age, site of myocardial infarction, urinary sodium, atrial sizes, radionuclide left ventricular ejection fraction, workload, baseline and peak-exercise heart rate, baseline and peak-exercise rate-pressure product, duration of exercise. Also baseline atrial natriuretic factor concentrations were similar in both groups (ischaemic patients: 34.51 ± 15.73 pg/ml; nonischaemic patients: 27.17 ± 8.74 pg/ml, NS), while peak-exercise atrial natriuretic factor concentrations were higher in patients with exercise-induced myocardial ischaemia (112.31 ± 35.5 pg/ml) than in the others (80.46 ± 23.43 pg/ml) ( P < 0.05). After 15 minutes of recovery, plasma atrial natriuretic factor levels were still raised only in the ischaemic patients (63.3 ± 15.44 pg/ml, P < 0.01), returning to baseline after 30 minutes in both groups. In control subjects, the behaviour of atrial natriuretic factor resembled that of the patients without exercise-induced ischaemia, with a significant increase at peak-exercise (from baseline levels of 23.1 ± 10.5 pg/ml to peak-exercise levels of 91.3 ± 14.5 pg/ml, P < 0.0005) and a rapid return to baseline levels after 15 minutes of recovery (28.5 ± 10.6 pg/ml, NS). Plasma atrial natriuretic factor levels were significantly higher in patients with exercise-induced myocardial ischaemia than in controls both at peak-exercise ( P < 0.05) and after 15 minutes of recovery ( P < 0.01). In conclusion, our data confirm that plasma atrial natriuretic factor levels increase during exercise in patients after acute myocardial infarction. Furthermore, atrial natriuretic factor levels increase to a larger extent in patients developing exercise-induced myocardial ischaemia, also showing a delayed return to baseline as compared either to nonischaemic patients or to control subjects. This particular behaviour could be due to the onset of left ventricular dysfunction depending on myocardial ischaemia or to the direct stimulatory effect of myosite hypoxia on the release of atrial natriuretic factor.

Doxorubicin cardiotoxicity is associated with alterations of plasma levels of atrial natriuretic factor.

In order to determine the involvement of the atrial natriuretic factor (ANF) in a model of drug-induced cardiomyopathy, the effects of a single or repeated doses of doxorubicin on plasma ANF levels were examined. Female Wistar rats were treated with doxorubicin at two different schedules: a single 10 mg/kg iv dose or multiple 3 mg/kg iv doses once a week for 3 weeks; control groups were given vehicle (isotonic saline, 0.9% NaCl) intravenously. ANF was assayed in plasma by a specific and sensitive radioimmunoassay method and cardiac function was evaluated by monitoring of ECG and hemodynamic parameters. In the doxorubicin single-dose study plasma ANF values were measured during a period of 6 hours after dosing and were found to be significantly decreased at the 180th (12.5 +/- 2.9 pg/ml) and 360th minute (19.4 +/- 1.2 pg/ml) after dosing, compared to vehicle-treated animals (35.1 +/- 5.7 and 37.9 +/- 4.1 pg/ml, 180 and 360th minute, respectively). Rats treated with multiple doses of doxorubicin showed a significant increase in plasma ANF levels at the 21st (88.3 +/- 7.7 pg/ml) and 31st day (61.0 +/- 14.3 pg/ml) of the study compared to vehicle-treated animals at the same time points (41.8 +/- 8.0 and 26.5 +/- 7.2 pg/ml, respectively). At the 42nd day plasma ANF concentration in doxorubicin-treated rats was not significantly different from vehicle-treated rats. In both studies ANF level changes occurred in the setting of acute or chronic doxorubicin-induced cardiac damage, as evidenced by alterations of hemodynamic and ECG parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in atrial natriuretic factor and plasma renin activity in dogs infected with Trypanosoma brucei.

When beagle dogs were infected with Trypanosoma brucei, a marked reduction in the plasma concentration of atrial natriuretic factor (ANF) occurred in the terminal stage of the disease during weeks 3 and 4. At the same time there was an increase in plasma renin activity (PRA) after infection. Ultrastructural studies of the atria of these dogs demonstrated a reduction in ANF granules. The changes in ANF and PRA occurred in association with severe pancarditis and the development of heart failure. By impairing the ability of the heart and kidneys to regulate blood volume, the alterations in ANF and PRA could be involved in the pathogenesis of heart failure in T. brucei-infected dogs.

Normotensive normoxic men undergoing water diuresis fail to respond to stimulation of their peripheral arterial chemoreceptors by almitrine with an increase in plasma concentrations of atrial natriuretic factor.

The purpose of this study was to investigate the possible participation of atrial natriuretic factor (ANF) in the natriuretic and diuretic response occurring after stimulation of the peripheral arterial chemoreceptors by almitrine bismesylate in normoxic humans. The experiments were performed in 14 healthy male volunteers undergoing water diuresis. Each subject participated in two experiments. In one of them they ingested 100-mg almitrine at 12 p.m. The other study served as a control. Surprisingly, our subjects responded to almitrine with an elevation of urine flow only, whereas sodium excretion remained almost unchanged over the whole period of the experiments. As regards ANF plasma concentrations, no statistically significant differences between the control and the almitrine group could be observed. Moreover, no direct connection between ANF plasma concentrations and renal volume excretion was detectable. We conclude that a specific stimulation of peripheral arterial chemoreceptors by almitrine in humans undergoing water diuresis did not seem to raise ANF plasma concentrations as is the case at high altitude. Therefore we would suggest that there exists no specific reflex influence of these receptors on ANF release.

Effect of pacing on epinephrine-stimulated atrial natriuretic factor release.

Previous in vitro studies showed that epinephrine stimulation can induce atrial natriuretic factor (ANF) release only form the right atrium but not from the left. In addition, sinus node has been shown to play an important role in the release of ANF. In vitro studies were done in isolated left and right rat atria to determine if pacing can induce the left atria to release ANF during epinephrine stimulation. ANF concentrations in the perfusate were measured by a radioimmunoassay method. Epinephrine increased ANF release in the right atria (from 6.3 +/- 0.8 to 10.8 +/- 0.9 pg/min/mg), but not in the unpaced left atria (4.2 +/- 0.4 and 4.2 +/- 0.3 pg/min/mg). However, when the atria were paced, ANF release rose in both the left (from 6.2 +/- 0.5 to 11.5 +/- 1.4 pg/min/mg) and right (from 8.4 +/- 1.15 to 16.6 +/- 1.8 pg/min/mg) atria with epinephrine addition. These results suggest that atrial contraction and tension play an important role in epinephrine-stimulated ANF release.

Changes in atrial natriuretic factor processing and secretion with age.

The effect of age on atrial natriuretic factor (ANF) metabolism in the rat was studied. Plasma ANF levels rose with age. A positive correlation was found between age and plasma ANF levels. Molecular forms of ANF were also examined. alpha-ANF and gamma-ANF were present in the circulation. The ratio of gamma-ANF/alpha-ANF increased with age. The atria were isolated and perfused to determine the ANF secretion rate. The spontaneous release of ANF decreased with age. The released ANF mainly consisted of alpha-ANF with a small amount of gamma-ANF. The ratio of gamma-ANF/alpha-ANF in the effluent increased with age. ANF concentrations in the atria varied with age, but the molecular forms did not. gamma-ANF was the main form found in the atria. These results suggest that ANF secretion as well as post-transcriptional processing is altered with age.

Renal sites of action of physiological increases in plasma atrial natriuretic factor concentration in essential hypertension.

To investigate the renal, haemodynamic and neurohormonal responses to low-dose infusions of atrial natriuretic factor (ANF) in hypertensive humans. Ten patients with mild-to-moderate essential hypertension received incremental infusions of 3 and 6 ng/kg per min ANF or vehicle alone whilst on a constant dietary sodium intake. A 90-min basal clearance period was followed by two 2-h infusion periods, with urine collection in the last 90 min of each period. In each of the three clearance periods, glomerular filtration rate (GFR), renal tubular function, and the activity of the renin-angiotensin and sympathetic nervous systems were determined. The renal sites of ANF action were established by simultaneous measurements of 51Cr-ethylenediaminetetraacetate lithium and sodium clearances. Plasma concentrations of neurohormones were measured by radioimmunoassays. Plasma ANF concentrations increased by 1.6- and 2.5-fold during the lower and higher ANF infusion rates, respectively. Plasma cyclic guanosine monophosphate concentrations increased in parallel. ANF caused no changes in supine systolic and diastolic blood pressure or in heart rate. In contrast, haematocrit values increased progressively across the study. The renal effects of ANF administration were characterized by an unaltered GFR and significant increases in the renal clearances of lithium (a marker of end-proximal fluid delivery) and sodium when compared with vehicle infusions, whereas urine flow did not change. Estimated values of fractional proximal and distal tubular sodium reabsorption decreased significantly. Plasma concentration of active renin decreased during ANF infusions, but no significant changes in plasma levels of renin substrate, angiotensin I, angiotensin II or aldosterone were observed. A subtle activation of the sympathetic nervous system was indicated by a moderate increase in plasma noradrenaline during the ANF infusions. These results indicate that even small increases in plasma ANF, as can be found during physiological conditions, induce natriuresis in patients with essential hypertension by enhancing fluid delivery from the proximal tubules, in addition to impairing distal fractional sodium reabsorption. With minor exceptions, the ANF infusions caused qualitatively and quantitatively similar renal, haemodynamic and endocrine effects in the hypertensive patients as in a previously studied group of normotensive subjects.

Atrial natriuretic factor after cardiac surgery with cardiopulmonary bypass in children

To determine circulating atrial natriuretic factor (ANF) concentrations in the postoperative state and to define potential hemodynamic determinants of regional plasma ANF concentrations. Cohort study. Pediatric ICU in a university hospital. 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). 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. 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. 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.