Rise In Atrial Natriuretic Factor Research Articles

Humoral and Renal Response to Acute Volume Loading in Patients with Essential Hypertension

The effect of acute volume expansion (2 liters of saline solution in 2 h) on plasma concentrations of atrial natriuretic factor (ANF), plasma aldosterone concentration (PAC), plasma renin activity (PRA) and their relationship to the renal excretion of urine, sodium and potassium were studied in 6 control subjects and 7 patients with essential hypertension (EH) WHO stage I. Saline infusion provoked comparable rise in plasma ANF in both groups (from 2.98 +/- 0.45 to 12.36 +/- 1.74 pmol/l in the control subjects and from 3.80 +/- 0.72 to 15.78 +/- 2.06 pmol/l in EH patients), significant drop in PRA (from 0.915 +/- 0.419 to 0.256 +/- 0.127 nmol/l/h in controls and from 1.711 +/- 0.324 to 0.714 +/- 0.128 nmol/l/h in EH) and in PAC (from 0.30 +/- 0.07 to 0.14 +/- 0.03 nmol/l in control subjects and from 0.53 +/- 0.13 to 0.24 +/- 0.07 nmol/l in EH). The increase of plasma ANF concentrations after volume expansion might be involved in the suppression of PRA and PAC found after this stimulus. Similar increase in plasma ANF after saline infusion in both groups was associated with significantly greater urine and sodium excretion in EH than in controls. From these results it may be suggested that the acute volume expansion during saline infusion evokes a comparable release of ANF into circulation in both EH patients and controls. In EH patients, however, the similar rise in ANF is accompanied by a more pronounced diuretic and natriuretic response. This exaggerated natriuresis after acute volume and sodium loading cannot be explained solely by a rise in ANF.(ABSTRACT TRUNCATED AT 250 WORDS)

Characteristics of the Acute Rise of Atrial Natriuretic Factor During Ventricular Pacing

Previous studies have shown that peripheral venous levels of atrial natriuretic factor (ANF) are elevated during ventricular pacing as a result of asynchrony of atrial and ventricular contraction. However, the pattern by which ANF rises following institution of ventricular pacing has not been fully established and its physiologic consequences are unclear. Eight ambulatory patients in stable condition with dual-chamber pacemakers were studied. The pacemaker was reprogrammed from the dual-chamber to the ventricular pacing mode for 3 h, during which serial measurements were made of BP, heart rate and rhythm, levels of ANF, and plasma renin activity (PRA). ANF levels rose markedly but slowly following the onset of ventricular pacing, reaching levels as high as 694% of control. The rise occurred over the course of 120 min, at which time the average value for the group plateaued at 82.5 +/- 22.1 fmol/mL (mean +/- SEM) vs 25.3 +/- 4.5 fmol/mL at control (p < 0.01); there was, however, marked variability in individual responses. By contrast, levels of PRA remained remarkably stable. Average BP changes were small, although there was a trend in the later part of the study for systolic pressure to decrease. ANF levels rise markedly but gradually after institution of ventricular pacing and, hence, acute pacing studies must account for this delay in their design. The physiologic importance of the rise in ANF should be evaluated further since the rise in peptide levels may be associated with a decrease in systolic BP.

Effect of low dose beta blockers on atrial and ventricular (B type) natriuretic factor in heart failure: a double blind, randomised comparison of metoprolol and a third generation vasodilating beta blocker.

This study examines the acute effects of two differing beta adrenergic blocking agents (metoprolol and a third generation vasodilating beta blocker) on plasma concentrations of atrial natriuretic factor (ANF), brain (ventricular) natriuretic factor (BNF), and haemodynamic variables in patients with heart failure. University teaching hospital. 20 patients with impaired left ventricular systolic function [ejection fraction 32 (SEM 2.3)%] were randomised in a double blind manner to receive either oral metoprolol 6.25 mg twice daily or celiprolol 25 mg daily. Haemodynamic variables were evaluated by Swan-Ganz pulmonary artery catheter over 24 hours. ANF and BNF concentrations were measured at baseline, 5 h, and 24 h by radioimmunoassay. At baseline ANF and BNF concentrations were considerably raised compared to the normal range. Treatment with metoprolol caused ANF to rise further to 147% of the basal level at 5 h (P = 0.017) and 112% at 24 h (P = 0.029). This was associated with a small but non-significant rise in pulmonary capillary wedge pressure. Cardiac output and systemic vascular resistance were unchanged at 24 h. In contrast, after celiprolol ANF fell to 90% of basal levels at 5 h and to 74% of basal level at 24 h (P = 0.019), associated with a small but non-significant fall in pulmonary capillary wedge pressure [-3.3 (2.7) mm Hg] and systemic vascular resistance, and rise in cardiac output from 3.2 (0.2) to 4.0 (0.4) l/min (P = 0.04). BNF concentrations rose to 112% of baseline at 5 h (P = 0.09) after metoprolol but fell slightly, to 91% of baseline values, after celiprolol (NS). Metoprolol, even in very low doses (6.25 mg), produced a rise in ANF and BNF, although minimal haemodynamic changes were detected. In contrast, a vasodilating beta blocker was associated with a significant fall in ANF and BNF and a small rise in cardiac output. This study confirms both the advantages of vasodilating beta blockers over metoprolol for initial treatment of heart failure and the usefulness of ANF and BNF measurements for the assessment of drug effects in heart failure compared to traditional haemodynamic measurements.

Atrial wall tension changes and the release of atrial natriuretic factor on relief of cardiac tamponade

Cardiac tamponade causes elevation and equalization of cardiac filling pressures, sodium and water retention, and a paradoxically low plasma atrial natriuretic factor (ANF) concentration despite increased intraatrial pressures. Recent reports suggested that plasma ANF concentrations rise after relief of tamponade. The purposes of the present study were (1) to determine the time course and extent of ANF release on relief of cardiac tamponade; (2) to measure the atrial transmural wall pressures, atrial sizes, and atrial wall tension changes associated with relief of tamponade; and (3) to determine the biologic activity of elevated plasma ANF during and after relief of tamponade. We sampled blood for ANF and cyclic guanosine monophosphate (cGMP) immediately before and up to 24 hours after relief of cardiac tamponade in 10 patients. Atrial and pericardial pressures were measured immediately before and shortly after pericardiocentesis, and atrial dimensions were determined by two-dimensional echocardiography before and within 1 hour after the tap. Urine volumes were measured in 8-hour increments before and after the procedure. Relief of cardiac tamponade was associated with a prompt and massive increase in plasma ANF concentrations, reaching pharmacologically active levels. The rise in ANF was negatively correlated with atrial pressures but positively correlated with atrial transmural pressures, atrial size, and calculated wall tension. Plasma ANF levels peaked at 515 ± 95 pg/ml 40 minutes after relief of tamponade and leveled off at 140% to 180% of the pretap concentrations. Plasma cGMP exhibited a slightly delayed but similar time course to the rise in ANF levels, and urine flow rate increased fourfold in the 8 hours after relief of tamponade. We conclude that (1) the relief of cardiac tamponade stimulates the release of atrial natriuretic factor by increasing atrial transmural wall pressures, atrial size, and calculated wall tensions; (2) evidence for the biologic activity of the increased plasma ANF concentrations is provided by the temporal association of increased cGMP levels and increased urine flow rate; and (3) that the release of ANF is governed by changes in atrial transmural wall, pressures and calculated atrial wall tensions.

Prostaglandin F2 alpha mediates platelet-activating factor-stimulated atrial natriuretic factor release from the isolated rat heart.

Platelet-activating factor (PAF) and the prostaglandins have recently been shown to stimulate atrial natriuretic factor (ANF) secretion from the heart. As PAF also potentiates the release of cyclooxygenase products from isolated hearts, the role of these substances in PAF-induced ANF secretion was investigated. Using an isolated perfused rat heart preparation, cyclooxygenase inhibition by indomethacin or meclofenamic acid (10 microM for each) significantly attenuated the rise in ANF associated with PAF administration (2.5 nmol). Prostaglandin F2 alpha (PGF) produced an immediate and dose-dependent increase in ANF secretion, which was significant at 0.01 mumol and reached 348 +/- 66% over baseline values after a 1-mumol injection. Prostaglandin E2 (PGE) generated a much smaller 98 +/- 25% increase after a 1-mumol administration. Furthermore, PGF but not PGE was released from isolated hearts immediately after PAF administration. PGF release reached a maximum of 0.06 nmol/min g Heart-1 1 min after PAF stimulation and had returned to undetectable baseline values by 6 min. Cyclooxygenase inhibition abolished the release of PGF after PAF, in addition to attenuating (by 60-70%) the increased secretion of ANF after PAF injection. These results demonstrate very clearly that PGF is the major mediator for PAF-stimulated ANF secretion. Such an interaction may provide an alternative mechanism to atrial distension for the secretion of ANF in pathologies such as myocardial infarction, where autacoids such as PAF and the PGs are released from damaged cardiac muscle and elevated plasma levels of ANF are observed.

Haemodynamic and neurohumoral response in heart failure produced by rapid ventricular pacing.

The aim was to determine the exact sequence of hormone changes during the progression of fluid retention in a canine model of "congestive cardiac failure" induced by rapid right ventricular pacing, and during recovery when pacing is stopped. Rapid ventricular pacing at a rate of 250 pulses.min-1 was used in six mongrel dogs with implanted right ventricular pacemakers. Right heart haemodynamics were measured by means of Swan Ganz catheterisation, allowing flow measurement by thermodilution and pressure measurement by external manometry. Plasma renin activity, arginine vasopressin, and atrial natriuretic factor were assayed on venous blood samples by radioimmunoassay. Noradrenaline was assayed by high pressure liquid chromatography. The onset of rapid pacing was accompanied by a fall in cardiac output and a rise in pulmonary arterial, pulmonary capillary wedge, and right atrial pressures. Noradrenaline and atrial natriuretic factor rose. Plasma renin activity showed an initial fall followed by a rise, and arginine vasopressin was unchanged in the first 8 h. When rapid pacing was continued for a further 35 d, clinical signs of fluid retention appeared by day 28, by which time cardiac output had fallen, and central pressures risen further. Atrial natriuretic factor peaked at around 14 d whereas plasma renin activity, arginine vasopressin, and noradrenaline tended to reach a plateau at about d 20 and then to show further increases as clinical signs of fluid retention appeared; this was most marked with plasma renin activity. Cessation of pacing at d 35 caused a rapid reversal (increase) of cardiac output but a more gradual reversal (decrease) of right heart pressures over 5 d; only wedge pressure returned to base line. Arginine vasopressin and plasma renin activity fell rapidly to around 40% of the final pacing levels and reached basal values after 8 h and 48 h respectively. Noradrenaline fell after 8 h and reached basal levels in 5 d. Atrial natriuretic factor fell quickly by 60% after 8 h but remained above basal levels for 5 d. At the end of pacing, body weight fell rapidly in conjunction with a large diuresis. These findings are compatible with a major role of one or more of renin, vasopressin, and noradrenaline in the pathophysiology of the fluid retention of heart failure; the manifestations are not counteracted by the rise in atrial natriuretic factor.

The exercise-induced rise in atrial natriuretic factor is reduced by chronic angiotensin converting enzyme inhibition in patients with primary hypertension

The exercise-induced rise in atrial natriuretic factor is reduced by chronic angiotensin converting enzyme inhibition in patients with primary hypertension

Neither ventricles nor afterload relief influence the raised plasma atrial natriuretic factor induced by volume expansion in the spontaneously hypertensive rat

The aims were (1) to study the influence of afterload relief on the rise in atrial natriuretic factor (ANF) which occurs during acute volume expansion in the spontaneously hypertensive rat (SHR); (2) to assess the contribution of the atria and the ventricles to ANF release under these circumstances. In the first series of experiments, SHR were treated with captopril (150 mg.kg-1.d-1) orally for 10 d. Untreated SHR and Wistar-Kyoto (WKY) rats served as controls. Volume expansion, equivalent to 10% of the total blood volume, was performed three times with human plasma protein fraction at 15 min intervals on conscious animals. Some haemodynamic variables and plasma ANF were measured. Tissue ANF measurements were conducted on another series of treated and control SHR not submitted to volume expansion. In another series of experiments, conscious SHR and WKY rats were submitted to repetitive 30% volume expansion (three times at 15 min intervals). Non-expanded animals served as controls. At the end of the experiments, tissue ANF measurements were performed. All experiments were conducted on 15 week old SHR and WKY rats. Captopril treatment reduced systolic blood pressure and cardiac hypertrophy in SHR. During volume expansion, changes in left ventricular end diastolic pressure were greater in control SHR than in treated SHR or WKY rats. Central venous pressure was affected similarly by volume expansion in both SHR groups. Plasma ANF rises induced by volume expansion were equal in all groups. Captopril treatment had no effect on right or left auricular ANF content prior to volume expansion. Repetitive 30% expansion reduced both right and left auricular ANF concentrations to the same extent (approximately 300-1500 ng.mg-1 protein) in SHR and WKY groups. Ventricular ANF was not affected by volume expansion in SHR, whereas volume expanded WKY rats had higher right and left ventricular ANF concentrations than their non-expanded controls. (1) The increase in plasma ANF during volume expansion is not impaired in SHR with newly established hypertension; (2) captopril treatment decreases afterload and the changes in left ventricular end diastolic pressure during volume expansion in SHR, without affecting plasma ANF increases; (3) both the auricles, but not the ventricles, contribute to enhanced ANF secretion caused by acute volume expansion in SHR and WKY rats.

The exercise-induced rise in atrial natriuretic factor is reduced by chronic angiotensin converting enzyme inhibition in patients with primary hypertension

The exercise-induced rise in atrial natriuretic factor is reduced by chronic angiotensin converting enzyme inhibition in patients with primary hypertension

The Atriopeptidase Inhibitor UK 69,578 Increases Atrial Natriuretic Factor and Causes a Natriuresis in Normal Humans

The endopeptidase EC 3.4.24.11 (atriopeptidase) degrades atrial natriuretic factor (ANF). Intravenous administration of UK 69,578 (0.025 to 10.0 mg/kg), a new specific atriopeptidase inhibitor, in 16 normal volunteers produced a two- to three-fold rise in endogenous ANF. Peak levels were reached within 2 h declining to control values by 8 h. The rise in ANF was associated with an increase in urine volume and mean urinary sodium excretion rose from 64.9 mmoles/8 h after placebo to 116.1 mmoles/8 h after 10 mg/kg UK 69,578. Despite the natriuresis, plasma active renin concentration was suppressed for up to 8 h. We conclude that inhibition of the endopeptidase EC 3.4.24.11 in humans elevates endogenous ANF and causes a natriuresis and may offer a novel therapeutic approach to the treatment of hypertension and cardiac failure.

Fetal hypoxia elevates plasma atrial natriuretic factor concentration

Acute hypoxia in the fetus is associated with a reduction in fetal blood volume. We hypothesized that atrial natriuretic factor in the fetal circulation may be one of the factors that mediate this blood volume decrease. Thus the present study was designed to determine the effects of hypoxia on circulating concentrations of atrial natriuretic factor in fetal sheep and correlate these changes with fetal blood volume. Hypoxia was induced in chronically catheterized sheep fetuses by infusing nitrogen containing CO2 into the trachea of the ewe for 30 minutes. Fetal arterial Po2 decreased by 10.2 ± 1.3 (SE) mm Hg. Plasma atrial natriuretic factor concentration rose concurrently with the fall in Po2 such that atrial natriuretic factor increased to 565 ± 196 pg/ml from a basal level of 127 ± 13 pg/ml (p < 0.001). Fetal blood volume was reduced by 7.2% ± 2.1% and was significantly related to changes in atrial natriuretic factor levels (p < 0.0001). At the termination of hypoxia, Po2 returned to normal levels before plasma concentrations of atrial natriuretic factor fell to baseline values. Therefore fetal hypoxia appears to be a potent stimulus for elevating plasma concentration of atrial natriuretic factor in the fetus, and this rise in atrial natriuretic factor in the circulation may be partially responsible for the reduction in fetal blood volume observed during hypoxia.

The effect of hemorrhage and resuscitation on serum levels of immunoreactive atrial natriuretic factor.

To determine if atrial natriuretic factor (ANF) might have a role in blood volume regulation during hypovolemia, the serum level was measured before and after hemorrhage and resuscitation (RESUS) in a porcine shock model. Hemorrhage of 40% of the blood volume produced significant (p less than 0.01) decreases in mean arterial pressure, central venous pressure, and cardiac output and a significant increase in heart rate (HR), plasma renin activity, and catecholamines (p less than 0.01). Hemorrhage was also associated with a significant increase in ANF (p less than 0.05). All parameters except HR returned to baseline values with RESUS. The rise in ANF associated with moderate hemorrhage was unexpected, but may have been due to the profound tachycardia or decreased degradation during shock. Sodium excretion and urine flow increased significantly with RESUS without an associated increase in ANF, suggesting that ANF may not be involved in the early phase of postresuscitation diuresis.