Atrial Natriuretic Factor Values Research Articles

Atrial natriuretic factor increases peritoneal dialysis efficiency in nephrectomized rats

The effect of atrial natriuretic factor (ANF) on peritoneal dialysis was studied in bilaterally nephrectomized rats. ANF was injected prior to every dialysis exchange and blood samples were obtained before the instillation of the dialysis solution and during the collection of dialysates. Urea, creatinine, potassium, and sodium were determined in both plasma and dialysates. Results showed that ANF increased the plasma clearance of all studied solutes, probably through vasodilation. Solute clearances showed a gradual increase with each dialysis exchange in both control and experimental animals. Therefore, ANF plasma levels were assayed before, during, and after peritoneal dialysis in a control group of nephrectomized rats to determine whether ANF plasma levels were modified during dialysis. Plasma ANF values were higher during and after peritoneal dialysis, though basal levels were similar to those of non-nephrectomized rats. These results suggest the release of endogenous ANF from the cardiac atria during peritoneal dialysis. The present results suggest that ANF may be of potential interest in the clinical field to increase the efficiency of peritoneal dialysis in man.

Atrial natriuretic factor in gynecologic malignancy

To determine whether plasma atrial natriuretic factor (ANF) levels are different in patients with gynecologic malignancy compared with those in healthy, nonpregnant women, and if differences do exist, whether chemotherapy plays a role. We compared the plasma levels of ANF in nonpregnant women free of malignancy (group 1, n = 25) and in patients with malignancy receiving at least one course of platinum-based chemotherapy (group 2, n = 32). To differentiate the contributory role of chemotherapy, another group of patients (group 3, n = 18) was studied before the initiation of chemotherapy. The ANF values (mean +/- standard error [SE]) in groups 1, 2, and 3 were 7.3 +/- 0.3, 13.8 +/- 0.8, and 14.6 +/- 1.8 fmol/mL of plasma, respectively. Significant differences (P < or = .001) occurred between groups 1 and 2 and 1 and 3, but not between 2 and 3. In comparing groups 2 and 3 for a specific type of cancer, there were no significant differences. The respective values (mean +/- SE) for endometrial, ovarian, and cervical cancer before chemotherapy were 9.9 +/- 1.7, 15.05 +/- 2.6, and 18.5 +/- 4.3 fmol/mL. After chemotherapy, the values remained at 9.3 +/- 1.5, 15.03 +/- 1.06, and 14.6 +/- 2.2 fmol/mL, respectively. Plasma ANF levels in gynecologic cancer patients were significantly higher than those in healthy, nonpregnant women. Levels were higher before chemotherapy started, thus negating the idea that chemotherapy may initiate the production and release of ANF.

Human natriuretic factor in cirrhotic patients undergoing orthotopic liver transplantation

We measured the plasma levels of atrial natriuretic factor (ANF) during orthotopic liver transplantation (OLT) in eight adult patients with cirrhosis and ascites. The aim of this study was to determine whether significant differences in ANF concentration may be detected during the individual phases of OLT and to correlate these changes with hemodynamics. In each patient a hemodynamic assessment was achieved using a Swan-Ganz fiber optic catheter for continuous monitoring of cardiac output (CO), systemic vascular resistance index (SVRI), right filling pressure as assessed by central venous pressure (CVP), and left filling pressure by means of pulmonary arterial wedge pressure (PAWP). During reperfusion a clear-cut increase in ANF values was observed (P < 0.05). Concurrently, an increase in CVP (P < 0.05) and a decrease in SVRI were observed without any significant increase in diuresis. These data suggest that ANF might play a role in the development of the reperfusion syndrome.

Endogenous opioid system and atrial natriuretic factor in normotensive offspring of hypertensive parents at rest and during exercise test

To investigate the effects of the endogenous opioid system on plasma atrial natriuretic factor (ANF) levels during sympathetic hyperactivity. We studied the young normotensive offspring of parents who both had essential hypertension, who are characterized by a hyperactive sympathetic nervous system. We assessed plasma beta-endorphin, met-enkephalin, dynorphin B, ANF and noradrenaline levels, blood pressure and heart rate values in eight normotensive offspring and in 10 young normotensive subjects with no family history of hypertension (controls) at rest and during two exercise tests: the first test performed with the infusion of placebo (1.5 ml/min saline) and the second test with the infusion of an opioid antagonist (9.5 micrograms/kg per min naloxone hydrochloride). ANF and opioids were radioimmunoassayed after chromatographic pre-extraction. At rest plasma met-enkephalin, dynorphin B, ANF and noradrenaline values in the normotensive offspring were significantly higher than in the controls. Exercise with placebo significantly raised all hormonal and haemodynamic parameters in the two groups. This increase was significantly higher in the normotensive offspring than in the controls. Naloxone did not modify any parameter in either group at rest, but it enhanced further the rise in plasma noradrenaline levels induced by exercise in both groups. A similar effect of naloxone during exercise was observed for plasma ANF levels in the normotensive offspring. Our findings show that plasma met-enkephalin, dynorphin B, ANF and noradrenaline levels at rest and during exercise are higher in normotensive offspring than in controls. The effects of naloxone indicate that in normotensive offspring at rest the opioid system does not affect ANF release, whereas during exercise it attenuates ANF hypersecretion, possibly by reducing noradrenaline release.

Relationship between hemodynamic changes and blood hormone concentrations after cardiac surgery in children with congenital heart disease

To evaluate changes in atrial natriuretic factor in relation to modifications in hemodynamic variables, and to evaluate hormones determining salt and water metabolism after heart surgery in children with congenital heart disease. Prospective study. Medical-surgical pediatric intensive care unit (ICU) in a tertiary referral center. Sixty-five infants and children admitted to the pediatric ICU with congenital heart disease who underwent cardiac surgery with extracorporeal circulation. The control group consisted of 48 children undergoing noncardiac surgical interventions, without a history of cardiac disease and with normal hemodynamic variables. Patients with congenital heart disease were distributed into two groups, according to hemodynamic variables. Group 1 consisted of patients with normal pulmonary blood flow (pulmonary/systemic blood flow ratio of < 2, pulmonary arterial systolic pressure of < 35 mm Hg, pulmonary arterial systolic pressure/aortic systolic pressure ratio of < 0.35). Group 2 consisted of patients with relatively increased pulmonary blood flow (pulmonary/systemic blood flow ratio of > 2.5, pulmonary arterial systolic pressure of > 65 mm Hg, pulmonary arterial systolic pressure/aortic systolic pressure ratio of > 0.75). Blood samples were obtained 24 hrs before, and 24 and 48 hrs after surgery. Hormone determinations included plasma concentrations of atrial natriuretic factor, vasopressin, plasma renin activity, corticotropin, cortisol, and aldosterone. Hemodynamic measurements were recorded simultaneously with blood sampling. Twenty-four hours before surgery, plasma concentrations of atrial natriuretic factor were higher in congenital heart disease patients than in the control group (67.36 +/- 93.44 vs. 15.11 +/- 8.29 pmol/L) (p < .001). Plasma concentrations of atrial natriuretic factor were 57.12 +/- 82.20 and 74.63 +/- 101.03 pmol/L in groups 1 and 2, respectively. Before surgery, in group 2 patients, there was a significant correlation between mean right atrial pressure and atrial natriuretic factor (r2 = .64; p < .001), vasopressin (r2 = .55; p < .001), cortisol (r2 = .43; p < .01), corticotropin (r2 = .53; p < .01), and aldosterone (r2 = .57, p < .001). None of these correlations were observed in group 1. However, 24 hrs after surgery, we found a significant correlation between diastolic blood pressure and atrial natriuretic factor in group 1. Plasma concentrations of atrial natriuretic factor did not change significantly after surgery. After surgery, the correlation between mean right atrial pressure and the various hormone concentrations persisted at 24 hrs (p < .05), but not at 48 hrs. Twenty-four hours after surgery, patients with a central venous pressure of > 7 mm Hg showed higher concentrations of atrial natriuretic factor than those patients with central venous pressures of < 7 mm Hg (p < .05). However, there was a large overlap of atrial natriuretic factor values between the two groups. Patients with congenital heart disease have increased plasma concentrations of atrial natriuretic factor. During the early postoperative period, in patients with a more severe degree of congenital heart disease, the increase in central venous pressure correlated with higher plasma concentrations of atrial natriuretic factor. High pulmonary blood flow was associated with an increase in plasma renin activity and serum aldosterone, and an increased secretion of atrial natriuretic factor.

Effect of ACE inhibitors on atrial natriuretic factor in the brains of rats with reduced renal mass

We tested the effect of renal insufficiency, with and without angiotensin (Ang) converting enzyme (ACE) inhibition, on blood and brain atrial natriuretic factor (ANF) in rats. Two ACEs, one which penetrates into the CNS and one which does not, were used to distinguish between peripheral and central ACE effects. Rats underwent 5/6 nephrectomy (5/6-NPX) by ligation of renal arterial branches. After seven days, 28 5/6-NPX rats received lisinopril 20 mg/kg/day and 28 5/6-NPX rats received quinapril 30 mg/kg/day orally for five days, while 28 5/6-NPX control rats and 28 sham rats did not. Body weight, blood pressure, drinking and urine volume were monitored. At sacrifice, urine, plasma, and brain tissue was collected. ANF in 16 brain areas was measured by radioimmunoassay. 5/6-NPX resulted in increased blood pressure, increased urine volume, proteinuria, and increased drinking. Both ACEs lowered blood pressure to sham values and decreased proteinuria. Both ACEs increased plasma renin activity and decreased plasma ANF. However, only lisinopril decreased drinking and urine volume. 5/6-NPX increased ANF values in six brain areas, namely the periventricular preoptic nucleus, the arcuate nucleus, the perifornical nucleus, the periventricular hypothalamic nucleus, the paraventricular nucleus, and the dorsal raphe nucleus compared to sham rats. These same increases in brain ANF were also observed in 5/6-NPX rats given quinapril, compared to shams. However, lisinopril lowered ANF to sham levels in the periventricular preoptic nucleus, the arcuate nucleus, and the perifornical nucleus. In the three additional brain areas, namely the periventricular hypothalamic nucleus, the paraventricular nucleus, and the dorsal raphe nucleus, lisinopril did not effect the elevated ANF concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between plasma atrial natriuretic factor and opioid peptide levels in healthy subjects and in patients with acute congestive heart failure.

We evaluated plasma atrial natriuretic factor (ANF), beta-endorphin, met-enkephalin, dynorphin and noradrenaline levels in 20 healthy subjects and 20 acute congestive heart failure (CHF) patients. In all acute CHF patients plasma values of these hormones were higher than in healthy subjects. The hormonal pattern differed in patients with the more severe acute CHF (group 1) from patients with less severe acute CHF (group 2) (ANF 53.8 +/- 1.0 vs 34.6 +/- 1.5 pg.ml-1, noradrenaline 563.8 +/- 13.4 vs 202.4 +/- 10.6 pg.ml-1, met-enkephalin 41.0 +/- 3.2 vs 17.0 +/- 1.6 fmol.ml-1, dynorphin 46.8 +/- 3.7 vs 25.2 +/- 2.0 fmol.ml-1, P < 0.01; beta-endorphin 50.6 +/- 5.2 vs 41.8 +/- 4.1 fmol.ml-1,ns). Administration of an opioid antagonist (naloxone, 8 mg i.v.) did not modify ANF or noradrenaline concentration in healthy subjects. In group 1 naloxone administration significantly raised ANF (68.0 +/- 1.4 pg.ml-1), noradrenaline (776.6 +/- 18.7 pg.ml-1), blood pressure and heart rate, whereas in group 2 it significantly decreased ANF values (21.9 +/- 0.5 pg.ml-1) and did not modify the other parameters. Our findings suggest that the opioid system affects ANF release in acute CHF. In patients with severe CHF opioid peptides may attenuate ANF secretion reducing noradrenergic stimulation. On the other hand, when CHF is less severe and the sympathetic activity is moderate, opioid peptides may directly stimulate ANF secretion.

Atrial natriuretic factor and changes in the aldosterone response to angiotensin II in sodium depleted dogs.

The effects of physiological shifts in plasma atrial natriuretic factor (ANF) concentrations on angiotensin II/aldosterone relationships during changes in sodium status were assessed in 6 conscious beagle dogs. Incremental infusions of angiotensin II (3, 9 and 27ng/kg/min) were administered on three occasions. The animals were studied in sodium replete and deplete states and on a third occasion, again while sodium deplete, with a background constant low-dose infusion of ANF (1.5pmol/kg/min) sufficient to enhance the low endogenous plasma ANF values observed in sodium depletion to match those observed in the sodium replete state. Sodium depletion caused a leftward shift and steepened the slope of the relationship between achieved arterial angiotensin II concentrations and the plasma aldosterone response. This effect was significantly attenuated (approximately 50%) by the low dose ANF infusions which tended to flatten the slope of the angiotensin II/aldosterone curve (ns) and shifted it significantly to the right (p < 0.05). These data suggest subtle shifts in endogenous levels of plasma ANF, accompanying changes in sodium status, are a major contributor to the associated alterations in angiotensin II/aldosterone relationships. Low dose ANF also significantly reduced the effect of angiotensin II on arterial pressures but did not alter natriuresis.

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.

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)

Exaggerated ANF response to exercise in middle-aged vs. young runners

Hormonal, electrolyte, and renal responses were measured before, during, and after a marathon (42.2 km) in 14 runners: 8 young (Y) (mean age 27.8 yr) and 6 middle aged (MA) (mean aged 46.7 yr). No differences between groups in prerun values for heart rate (HR), plasma osmolality (OSM), antidiuretic hormone (ADH), aldosterone (ALDO), atrial natriuretic factor (ANF), or plasma renin activity (PRA) were found. Renal and urinary measurements were also similar between groups before the marathon. After 10 km of running, both groups had significant increases in HR, ALDO, ANF, and PRA, while OSM, Na+, and ADH remained unchanged from prerun values. The increase in plasma ANF concentrations at this point was significantly greater in the MA subjects compared with the Y (mean increase 104.1 vs. 42.8 pg/ml, respectively; P less than 0.01). Immediate postmarathon values for OSM, ADH, and Na+ were significantly higher than initial values in both groups, while HR, PRA, and ALDO continued to increase above the elevated levels found at 10 km. ANF values immediately postmarathon remained higher than prerun concentrations but were significantly reduced from those obtained at 10 km. In contrast, HR continued to rise until the completion of the run. These data are consistent with recent reports of an exaggerated ANF response in older subjects in response to central blood volume expansion.

Vasodilatory action of endogenous atrial natriuretic factor in a rat model of chronic heart failure as determined by monoclonal ANF antibody.

Elucidation of the role of (elevated) endogenous atrial natriuretic factor (ANF) in chronic heart failure has been hampered by a lack of specific inhibitors. We used a newly developed monoclonal antibody that has been shown to specifically block both exogenously and endogenously released ANF in vivo. For assessment of the vasodilatory action of ANF in chronic heart failure, either this antibody against ANF or ascites (control serum) was injected in rats with myocardial infarction and failure and in sham animals. Ascites did not alter central hemodynamics in either the sham or infarcted group. Antibody significantly increased right atrial pressure, left ventricular end-diastolic pressure, and systemic vascular resistance (SVR) in the infarction group but did not affect these variables in the sham group. Because renal blood flow, as measured by radioactive microspheres, decreased significantly in all four groups, probably due to nonspecific renal vasoconstrictor effects of the ascites, a separate group of infarcted animals was treated with purified ANF antibody (devoid of nonspecific effects) or mouse IgG as a control injection. In these animals, right atrial pressure increased from 1.1 +/- 0.7 to 2.6 +/- 0.7 mm Hg (p less than 0.001). Although SVR, renal blood flow velocity (measured by Doppler probe), and renal vascular resistance did not change in the infarcted animals after administration of purified ANF antibody, a significant correlation was found between baseline plasma ANF values and the change in SVR exerted by purified ANF antibody (r = 0.758, p less than 0.02, n = 9); that is, SVR increased in rats with high baseline plasma ANF (greater than 350 pg/ml), but decreased in animals with plasma ANF less than 200 pg/ml. These results suggest that moderately elevated endogenous plasma ANF levels in chronic heart failure do affect central hemodynamics, primarily by reducing venous pressure (e.g., by decreasing intravascular volume or by venous dilation). Arterial vasodilation, however, appears to emerge when plasma ANF is greatly increased.

Solid-phase double-antibody radio-immunoassay for atrial natriuretic factor

A solid-phase radio-immunoassay for the determination of atrial natriuretic factor (ANF) in human plasma is described. Iodination of alpha hANF was carried out with the iodogen method. Purification of radio-iodinated alpha hANF was performed by chromatography on disposable columns of DEAE-Sephadex A-25. Studies of immunoreactivity and the elution pattern on HPLC showed perfect stability of the labelled compounds. The tracer was usable for 28 weeks after preparation, and the batch-to-batch variation in the quality of the tracer was satisfactory. Immunoreactive ANF was extracted from human plasma with Sep-Pak C18 cartridges. Recovery of alpha hANF added to whole blood was 85 +/- 12% (mean +/- SD, n = 12). The sensitivity of the radio-immunoassay was 1.6 pg/tube, equivalent to 1 pg/ml plasma when assaying the extract from 4 ml plasma. Mean plasma ANF values in normal subjects in the supine position was 23 +/- 12 pg/ml (mean +/- SD, n = 21).

Correlation of Patent Ductus Arteriosus Shunting with Plasma Atrial Natriuretic Factor Concentration in Preterm Infants with Respiratory Distress Syndrome

The concentration of plasma atrial natriuretic factor (ANF) and the mechanism for its secretion were investigated in 17 preterm infants with respiratory distress. Their mean gestational age was 29 wk and wt 1250 g. The infants were followed during the first week of life by sequential Doppler ultrasound studies. Ductal openness versus closure and amount of ductal flow were correlated with plasma ANF concentrations. In a subset of 10 infants, sequential Doppler color flow mapping was used to quantify the ductal flow. During the first 72 h, plasma ANF was high, 361 pg/mL; it decreased to 96 pg/mL by the end of the 1st wk. The ANF level was significantly higher when the ductus was open than closed (393 versus 123 pg/mL, p less than 0.05). In patients with open ductus and bidirectional foramen ovale shunting (n = 3) ANF was 567 pg/mL and in those with left-to-right shunt 355 pg/mL (n 15, NS). The left atrial size, i.e. the left atrial to aortic root ratio, correlated with the amount of ductal shunting (r = 0.63, p less than 0.01) and with ANF concentration (r = 0.46, p less than 0.02). The correlation of ANF values and the magnitude of left-to-right ductal shunting assessed by color flow mapping was highly significant (r = 0.66, p less than 0.001). In these patients, the elevation of ANF is reflective of ductal flow.

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, atria[ size and peripheral resistance were independent predictors. Eight patients with elevated atrial natriuretic factor values (>25 fmo/ml) were significantly (p < 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 < 0.001), whereas it was positively related to the proportional contribution of atria[ systole to left ventricular filling in hypertensive patients (r = 0.77; p < 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.

The effect of subarachnoid hemorrhage on blood and CSF atrial natriuretic factor

Atrial natriuretic factor (ANF) is a diuretic natriuretic peptide hormone produced by both the heart and brain which has been postulated to play a role in the hemodynamic and sodium instability that frequently follows subarachnoid hemorrhage (SAH). Levels of ANF were measured in 12 patients with nontraumatic SAH and nine control patients with unruptured cerebral aneurysms. At surgery, the mean plasma ANF level (+/- standard deviation) of the SAH group was significantly higher than that of the control group (158.1 +/- 83.8 vs. 57.8 +/- 45.3 pg/ml, respectively; p = 0.01). There was no significant difference in serum sodium concentration, blood pressure, or central venous pressure between these groups. Nine patients with SAH due to aneurysm rupture had plasma ANF levels similar to those in three patients with SAH due to other causes. Four patients with moderate to severe SAH had significantly higher mean cerebrospinal fluid (CSF) ANF values (17.7 +/- 12.8 pg/ml) than five patients with minimal SAH (0.6 +/- 0.9 pg/ml) or the control group of nine patients (3.7 +/- 1.3 pg/ml) (p less than 0.05). Five patients with moderate to severe SAH had significantly higher plasma ANF values (202.6 +/- 72.2 pg/ml) than five with minimal SAH (86.8 +/- 29.2 pg/ml) or the control group (57.8 +/- 45.3 pg/ml) (p less than 0.05). Plasma ANF values were substantially higher than CSF ANF content in the SAH group (p less than 0.01) and in the control group (p = 0.05). From these data it is concluded that: 1) plasma ANF is elevated significantly after SAH; 2) this rise appears unrelated to the cause of hemorrhage, serum sodium concentration, blood pressure, or central venous pressure, but is related to the extent of the hemorrhage; 3) ANF concentrations in the CSF are significantly lower than in plasma, and are elevated after moderate to severe SAH; and 4) the source of CSF ANF is probably the plasma, and the source of plasma ANF is likely the heart.

Effect of a Total Artificial Heart on Adaptive Hormonal Responses in Humans with End-Stage Heart Failure

The J-7 total artificial heart (TAH) can restore normal vascular hemodynamics in humans treated for end-stage heart failure, but less is known regarding its effect on hormones elevated under these conditions. A 49-year-old man with NYHA Class IV end-stage heart failure received a J-7-70 TAH as a bridge to transplantation. Pre-TAH cardiac index was less than 2 L/min/m2 with end organ dysfunction, increased venous and pulmonary pressures, and a low arterial pressure. The TAH provided an immediate cardiac index greater than 3 L/min/m2 with normal hemodynamics and organ function. Pre-TAH renin, aldosterone, and atrial natriuretic factor (ANF) levels were markedly elevated: 147 ng/dl, 29.4 ng/dl, and 380 pg/ml, respectively. All values declined dramatically by the fifth postoperative day, with the aldosterone and ANF values returning to normal at 11.5 ng/dl and 37 pg/ml, respectively. Renin levels reached normal values by the fourth postoperative week. Once normal values were obtained, they remained in this range for the 57 days of TAH function. The TAH, used in end-stage heart failure, restores normal hemodynamics and compensatory hormonal levels. These hormones can be used as indicators of proper TAH function in such patients.

Echocardiographic Measurements and Plasma Levels of Atrial Natriuretic Factor

Summary: Atrial distension and pressure have been reported to be important for the release of atrial natriuretic factor (ANF) into the circulation. However, in mild essential hypertension, we have been unable to demonstrate an increase in plasma levels of ANF. To evaluate more precisely the lack of increase of ANF, we measured echocardiographically the diameters of the cardiac chambers and correlated these measurements with ANF values in normal subjects (n = 25), in patients with untreated essential hypertension (n = 20), and in patients with treated essential hypertension (n × 27). The plasma values of ANF were 21.9 ± 2.8 pg/ml in the normal controls, 20.4 ± 2.2 pg/ml in patients with untreated mild essential hypertension, and 32.6 ± 2.8 pg/ml in patients with treated but uncontrolled essential hypertension (p < 0.05). The plasma values of cGMP were 4.53 ± 0.56 pmol/ml in the normals, 5.41 ± 0.57 pmol/ml in the patients with untreated essential hypertension, and 6.76 ± 0.58 pmol/ml in treated essential hypertension (p < 0.05). There were no significant differences in the size of the cardiac chambers between the three groups, except for the size of the right atrium, but there was a correlation between the ANF values and the size of the left atria (r = 0.29, p = 0.01, n = 72), as well as with the size of the interventricular septum (IVS) in systole (r = 0.36, p = 0.002, n = 72). Since ANF levels are similar in mild untreated essential hypertension and normal volunteers, the ANF plasma levels could be a better reflection of the impact of the blood pressure on the myocardium than the level of blood pressure itself and indicate in patients the degree of cardiac impairment. On the other hand, there seems to be definitely an effect of treatment on the levels of ANF.

Atrial natriuretic factor in hypertensive and normotensive insulin-dependent diabetics

Since insulin increases renal sodium reabsorption, hyperinsulinaemia in insulin-treated insulin-dependent diabetes mellitus might lead to sodium retention and, in turn, increase atrial natriuretic factor (ANF) values. We investigated ANF levels in insulin-dependent diabetes mellitus with and without hypertension. We infused saline (2 mmol/kg per 90 min) in nine normotensive controls, eight normotensive diabetics, seven hypertensive controls and six hypertensive diabetics during the imposition of a euglycaemic glucose clamp with an artificial pancreas. Baseline ANF values were higher in the normotensive and hypertensive diabetics than in the normotensive and hypertensive controls. During a sodium load the sodium excretion rate increased significantly in controls but not in the diabetic groups. The ANF pattern was similar, values being significantly increased in controls and unchanged in diabetic patients. We conclude that euglycaemic, slightly hyperinsulinaemic, insulin-dependent diabetes mellitus patients with and without hypertension are characterized by higher baseline ANF values and an impaired response to an acute saline load as shown by the sodium excretion rate and the plasma ANF concentration.

Blunting of atrial natriuretic factor response to volume expansion by benazepril in hypertensive patients

To verify the hypothesis that the angiotensin converting enzyme (ACE) level may affect the metabolism of circulating atrial natriuretic factor (ANF), the acute and chronic effects of benazepril on plasma ANF levels were studied in hypertensive patients under basal conditions and in response to acute volume expansion. Ten essential hypertensives entered a double-blind crossover study, and were randomly allocated either to placebo or to 10 mg benazepril orally once a day for 2 days; after a placebo washout period of 2 days the groups were crossed over. On the second day of each crossover period, volume expansion was induced by infusing 1 litre saline in 30 min, and blood samples for ANF measurements were drawn at times -5, 0, 5, 15, 30, 35, 40, 50 and 60 min. Oral benazepril at 10 mg/day was then given to all patients for 4 weeks, and the volume expansion with saline was repeated. After the 2-day acute benazepril treatment, blood pressure fell from 166.1 +/- 3.6/105.1 +/- 0.9 to 140.1 +/- 4.6/85.6 +/- 2.1 mmHg (P less than 0.01 for both systolic and diastolic blood pressure), whereas ANF fell from 29.4 +/- 3.6 to 24.1 +/- 3.7 pg/ml (NS) after the acute benazepril treatment and to 17.7 +/- 3.6 pg/ml (P less than 0.01) after the chronic benazepril treatment. The volume expansion itself did not induce significant changes in mean arterial pressure, either during the placebo treatment or during the acute chronic benazepril treatment. The rise in ANF values in response to saline infusion during placebo was prompt, beginning at min 15 and reaching a maximum at min 40.(ABSTRACT TRUNCATED AT 250 WORDS)