Plasma ANF Levels Research Articles

Increased Plasma Atrial Natriuretic Factor in Catecholamine-Producing Tumor Patients

The aim of this study was to evaluate plasma levels of ANF in patients with catecholamine-secreting tumors with and without hypertension and to relate ANF secretion to levels of plasma and urinary catecholamines and blood pressure. Twenty-one pheochromocytoma (15 with sustained, 6 with paroxysmal hypertension), 6 neuroblastoma (1 hypertensive) patients and 28 aged-matched controls were studied in basal conditions. Plasma and urinary norepinephrine (NE),epinephrine (E), dopamine (DA) and DOPA were determined by HPLC-ED and plasma ANF by RIA. Both neuroblastoma and pheochromocytoma patients had significantly higher plasma ANF levels than controls. Neuroblastomas showed higher ANF concentration than pheochromocytomas. No differences were found in plasma ANF between hypertensive and normotensive patients. Pheochromocytomas with ANF levels within the normal range had plasma and urinary NE and urinary DA and DOPA levels significantly higher than patients with

Heredity and obesity-associated hypertension: impact of hormonal characteristics and left ventricular mass.

To investigate the influence of heredity on obesity-associated hypertension, we evaluated casual and 24-h blood pressure, left ventricular mass and some metabolic and hormonal measurements in normotensive obese subjects. Healthy, normotensive obese subjects (n = 81) with positive or negative family history of hypertension were studied. Both groups were also subdivided according to a positive or a negative family history of obesity. Accordingly, 45 obese subjects had a positive family history of hypertension, 25 of these having a positive (subgroup A) and 20 having a negative family history of obesity (subgroup B). The other 36 obese subjects had a negative family history of hypertension, 19 of these having a positive (subgroup C) and 17 having a negative family history of obesity (subgroup D). Casual and 24-h systolic (SBP), diastolic (DBP) and mean blood pressure (MBP) were evaluated. Serum fasting blood sugar, total cholesterol and triglycerides levels, urinary excretion of sodium, immunoreactive fasting insulin, plasma ANF levels, plasma renin activity (PRA), plasma aldosterone level, plasma adrenaline and noradrenaline levels and echocardiographic total left ventricular mass (LVM) and LVM:height ratio were also calculated. Twenty-four-hour DBP, 24-h MBP, LVM, LVM:height ratio, total cholesterol and PRA values were significantly higher in normotensive obese offspring of hypertensive parents than in obese offspring of normotensive parents. Twenty-four-hour DBP and MBP, LVM, LVM:height ratio, insulin level, insulin:glucose ratio and PRA were significantly higher in subgroup A than in subgroup B. Fasting blood sugar level, 24-h DBP and MBP, insulin level, insulin:glucose ratio, PRA, noradrenaline, adrenaline and plasma aldosterone levels were significantly higher in subgroup C than in subgroup D. Multivariate analysis also indicated that 24-h MBP and PRA levels were significantly influenced by the association between a positive family history of hypertension and obesity. The present results suggest that a family history of obesity might increase the risk of developing hypertension in obese subjects. An elevated PRA may precede the development of hypertension in obese subjects who are at risk for developing hypertension.

Atrial natriuretic factor in ovine pregnancy: plasma levels, molecular forms and biological activity

Pregnancy is associated with hypervolemia and elevated plasma ANF, but the time course over which ANF increases and the mechanisms that control plasma ANF levels are unclear. Plasma ANF was measured in 12 nonpregnant and 16 pregnant sheep at various gestational ages. ANF was elevated at 30–35 days of pregnancy ( 15.7±1.4 vs. 22.9±3.4 fmol/ml , P=0.04), but did not increase further with the advance of gestation. Tissue content of ANF was unchanged in the right atrium, left atrium, renal cortex, renal medulla, adrenals and lungs, but ovarian ANF content was increased during pregnancy ( 9.2±2.2 vs. 67.2±23.2 fmol/mg protein, P=0.003). However, the ovarian tissue ANF concentration was less than 0.2% of that in the atria during pregnancy. HPLC of plasma from both nonpregnant and pregnant ewes revealed the presence of a single peak that elutes in parallel with synthetic human ANF. HPLC of atrial and lung tissue homogenates revealed multiple peaks that may represent different molecular forms of ANF. The biological activity of ANF in the plasma of pregnant ewes was reduced to 23% of nonpregnant levels. ANF in lung tissue was also biologically active, but that activity was reduced to 13% of nonpregnant levels. These data suggest that elevated plasma ANF in pregnancy is not secondary to increased atrial, renal, adrenal, ovarian or pulmonary contribution. Since we have previously shown that the metabolic clearance of ANF is not decreased, other extra-atrial sites may contribute to the increased plasma ANF during pregnancy. In addition, ovine pregnancy is associated with similar molecular forms of ANF but these exhibit reduced biological activity and may, therefore, alter volume regulation during pregnancy.

Differential Regulation of ANF-R2 Receptors Coupled to Adenylyl Cyclase in Cardiovascular Tissues in Hypertension

We have recently shown that ANF-R2 receptors are coupled to the adenylyl cyclase/cAMP system through inhibitory guanine nucleotide regulatory protein (Gi). The present studies were undertaken to investigate the regulation of ANF-R2 receptor-mediated inhibition of adenylyl cyclase in spontaneously hypertensive rats (SHR) which have been reported to have high plasma ANF levels. ANF99-126 inhibited adenylyl cyclase activity in a concentration dependent manner in both aorta and heart sarcolemma from SHR and age-matched Wistar-Kyoto (WKY) rats, however, the extent of inhibition was greater in SHR as compared to WKY. On the other hand, ANF99-126 also inhibited the adenylyl cyclase activity in rat platelets from WKY rats in a concentration dependent manner, however, the inhibition in SHR was completely attenuated. In addition GTP gamma S stimulated adenylyl cyclase activity by about 600% in aorta from WKY rats and about 300% in SHR. On the other hand, the GTP gamma S-stimulated adenylyl cyclase activity was higher in platelets from SHR as compared to WKY. The observed difference may be attributed to the differential alterations in ANF-R2 receptor number or postreceptor events or both. Nonetheless, these results indicate that ANF-R2 receptors in platelets from SHR are differentially regulated than those in heart and aorta.

Atrial natriuretic factor in pregnancy and pregnancy-induced hypertension

In normal pregnancy, cross-sectional clinical data do not consistently show plasma ANF concentration differences between early pregnancy and the nonpregnant state. Sequential data in the baboon (but not in rat) show a significant decrease in plasma ANF concentration and in cardiac filling pressures in early pregnancy. The latter data support the view that pregnancy is an underfill state secondary to a primary vasodilatation. Cross-sectional and longitudinal studies in normal pregnancy in humans show that plasma ANF levels tend rise to values that are, in the third trimester, higher than in the nonpregnant state. However, late postpartum sequential data (1.5-3 months) in humans do now show a significant drop in plasma ANF concentrations, suggesting that plasma ANF is not actually increased in normal pregnancy. In the baboon (but not in the rat) there is a steady rise in plasma ANF levels to values that are significantly higher in third trimester than before pregnancy. These data suggest that in human pregnancy, in contrast with the baboon, the plasma volume expansion induced by normal pregnancy is not sensed as such by the atria probably because of an isopressive adaptation of plasma volume to an enlarged vascular bed. However, acute decrease or increase of venous return induced by low sodium diet, changing position or infusion of isotonic saline are sensed as such by the atria in normal pregnancy as in the nonpregnant state.(ABSTRACT TRUNCATED AT 250 WORDS)

Developing essential hypertension: a syndrome involving ANF deficiency?

The pathogenesis of essential hypertension may possibly involve a deficiency in, or a decreased response to, endogenous vasodilator and natriuretic factor(s). Searching for hereditary or familial defects, it is plausible to evaluate blood pressure (BP) regulating factors in (yet) normotensive offspring of hypertensive parents (OHyp), some of whom are in fact in a stage of prehypertension. Studies by our group demonstrated that compared with healthy offspring of normotensive parents, OHyp have plasma atrial natriuretic (ANF) factor levels that are unaltered on a low salt intake but often fail to increase normally in response to a high salt intake. Plasma levels of cyclic GMP, the presumed second messenger of ANF, also may tend to be decreased in certain OHyp. On the other hand, renal excretory responses of cyclic GMP and electrolytes to ANF infused in "physiological" dose were unchanged in some OHyp tested so far. In borderline to moderate, uncomplicated essential hypertension, plasma ANF levels are often "normal." This may be inappropriately low relative to the existing BP, although the relationship of circulating ANF to atrial pressures in essential hypertension remains to be clarified. A conversion to higher plasma ANF values may occur with cardiac complications such as left ventricular hypertrophy, enlargement, dysfunction, or overt heart failure. Acute or short-term elevation of circulating ANF within the physiological and pathophysiological range by ANF infusion produces an exaggerated natriuresis and lowers BP in essential hypertensive patients. We postulate a syndrome of ANF deficiency, characterized by an impaired response of circulating ANF to high salt intake and by low cyclic GMP levels in certain yet normotensive offspring of essential hypertensive parents and by inappropriately "normal" plasma ANF in some patients with uncomplicated essential hypertension. At the stage of prehypertension, a disturbance in the ANF - cyclic GMP pathway may be expressed primarily at the circulatory rather than at the renal level. Hypertension-prone humans also tend to have an exaggerated vascular reactivity to norepinephrine. Whether the two disturbances may be interrelated is presently unknown. Both defects may potentially predispose to the development of essential hypertension. Relative ANF deficiency, an enhanced natriuretic response to ANF, and a sustained antihypertensive effect of infused ANF may represent a rational basis for treatment of essential hypertension with agents that activate the ANF system.

Platelet-activating factor stimulates the release of atrial natriuretic factor from the rat heart

Atrial natriuretic factor (alpha-ANF (99-126), ANF) is released from atrial cells following atrial distension, myocardial infarction and periods of ischaemic or tachyarrhythmias. In this report we demonstrate that platelet-activating factor (PAF) stimulates ANF release from the isolated perfused rat heart and following i.v. injection to conscious unrestrained rats. ANF release peaked at 145% above baseline following injection of 2.5 nmol PAF into the isolated heart while administration of 2 nmol in vivo produced a 135% increase in plasma ANF levels. The PAF receptor antagonist BN52021 (10 mumol/l) attenuated this stimulated release, with the results suggesting a role for PAF in ANF secretion following release from damaged myocardium or as a humoral factor originating from the kidney.

L'hypertension artérielle peut-elle être expliquée par une anomalie de sécrétion du facteur atrial natriurétique et de l'endothéline ?

Plasma ANF and endothelin levels were measured in normotensive and hypertensive pregnant women and in non-pregnant controls. If ANF levels were normal in pregnant women the results concerning endothelin may account for the prevention in hypertensive pregnancy of the vasodilatation occuring in normal pregnancy.

Atrial natriuretic factor in patients with acromegaly

In acromegaly the plasma volume is chronically elevated and it returns to normal when the disease is successfully treated. To define the role of ANF in such a chronic disorder of extracellular fluid volume homeostasis the plasma level was assayed in 37 acromegalic patients with active or inactive (successfully treated) disease. Five patients were studied before and after therapy. The effects of acute change in sodium-fluid status on plasma ANF levels was examined in 7 active and 4 inactive acromegalic patients and in 7 healthy subjects. As compared to 14 patients with inactive acromegaly, 23 patients with active acromegaly had an expanded plasma volume (n = 12; 50.1 vs 37.6 ml.kg-1 BW) and an increased blood concentration of growth hormone (n = 23; 22.5 vs 2.1 ng.ml-1). Plasma ANF concentrations in active and inactive acromegalic patients (33.2 and 26.6 pg.ml-1, respectively) did not differ significantly from one another or from the level in the controls (26.9 pg.ml-1). In those patients there was no correlation between plasma volume and ANF level. Infusion of 21 isotonic saline in 2 h led to a similar, significant increase in ANF levels in active (from 26.2 to 72.4 pg.ml-1) and in inactive acromegalic patients (from 33.6 to 96.7 pg.ml-1) as well as in healthy subjects (from 21 to 70.6 pg.ml-1). Successful treatment reduced the plasma volume (from 49.2 to 35.8 ml.kg-1 BW) and growth hormone level (from 10.1 to 2.6 pg.ml-1), while the ANF level remained unchanged (from 33.8 to 35.5 pg.ml-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Caffeine-Induced Diuresis and Atrial Natriuretic Peptides

After a single-blind, randomized, cross-over protocol using decaffeinated coffee in a control experiment, the effect of an oral 250-mg caffeine dose on plasma immunoreactive atrial natriuretic peptide (ANF) was assessed in eight healthy students who had been on a methylxanthine-free diet for 1 week. One to 2 h after caffeine ingestion, both systolic blood pressure (SBP) and diastolic BP (DBP) increased by 12 mm Hg while heart rate (HR) also tended to increase. An increase in diuresis and in urinary sodium, potassium, and osmol excretion was observed within 1 h. Decaffeinated coffee induced no change in any of these parameters. Plasma epinephrine (EPI) increased gradually from 16.6 +/- 3.2 pg/ml (mean +/- SEM) to 45.1 +/- 7.9 pg/ml within 2 h after caffeine ingestion, but did not change after decaffeinated coffee (p less than 0.001). Plasma norepinephrine (NE), renin activity (PRA), aldosterone, and vasopressin remained unchanged. Plasma ANF was measured by radioimmunoassay (RIA) using an extremely sensitive antiserum (Kd = 10(-12) M) after rapid and virtually complete (90-103%) extraction from plasma. In 0.2 ml plasma, the theoretical detection limit is 1.1 fmol/ml. Normal plasma ANF concentrations in supine subjects were 17.9 +/- 8.1 fmol/ml (mean +/- SD) and 11.0 +/- 3.3 fmol/ml in subjects in the upright position. Plasma ANF levels were not affected by coffee drinking. In conclusion, by using a new and sensitive assay for plasma ANF, we did not find that caffeine-induced diuresis is mediated by ANF.

Atrial structure and plasma ANF levels in rats with chronic diabetes mellitus

Atrial structure and plasma ANF levels in rats with chronic diabetes mellitus

Natriuretic and diuretic effects of infusion of atrial natriuretic factor in conscious dogs

We studied the effects of 30-min infusions of the synthetic 25-amino acid atrial natriuretic factor [ANF-(102-126)] and the 28-amino acid ANF-(99-126) at 0.1 and 0.3 micrograms.kg-1.min-1 on urine flow rate, sodium excretion, and arterial pressure in conscious dogs. Each dose was administered on a separate day following a 1-h stabilization period. We also compared the effects of 60-min infusions of ANF, 0.01 micrograms.kg-1.min-1, or water infusion on separate days in conscious dogs. Arterial pressure was reduced in a dose-dependent fashion, reaching statistical significance at a dose of 0.3 micrograms.kg-1.min-1. During the 0.01-micrograms.kg-1.min-1 infusion, the plasma concentration of ANF rose approximately threefold (from 68 +/- 7 to 207 +/- 14 pg/ml), with no change in urine flow rate, sodium excretion, or arterial pressure. At a dose of 0.1 micrograms.kg-1.min-1, urine flow increased (P less than 0.05) by 0.41 +/- 0.15 ml/min, and sodium excretion rose by 72 +/- 24 mu eq/min, but not significantly, whereas plasma ANF levels rose to 1,236 +/- 229 pg/ml. At the highest dose of ANF (0.3 micrograms.kg-1.min-1) urine flow rose by 0.62 +/- 0.16 ml/min, P less than 0.05, and sodium excretion rose by 139 +/- 30 mu eq/min, P less than 0.05, whereas plasma levels of ANF rose to 2,436 +/- 320 pg/ml. In contrast, volume loading with dextran increased urine flow by 3.5 +/- 1.3 ml/min, P less than 0.05, and sodium excretion by 439 +/- 147 mu eq/min, P less than 0.05, whereas ANF rose to only 320 +/- 69 pg/ml. These results suggest that, in the conscious dog, ANF does not cause significant diuretic or natriuretic effects until plasma levels are markedly above those observed in physiological conditions. A possible explanation for the difference between this and previous studies is that the renal effects of ANF, at physiological plasma levels, are indirect and thus dependent on autonomic and hormonal (angiotensin, vasopressin, and aldosterone levels) factors governing the renal function of the animal.

Atrial natriuretic factor in human pathophysiology.

1. Evidence from numerous experiments incorporating central blood volume expansion and changes in sodium status supports atrial stretch as the prime determinant of ANF release. 2. Plasma ANF levels are the result of both secretion and clearance of the peptide. Clearance is altered by a number of factors, including changes in posture in normal man and is probably impaired in disease states with diminished renal and hepatic blood flow. 3. In normal subjects an inverse relationship exists between plasma ANF values and renin-angiotensin-aldosterone system activity. This relationship is lost and replaced by a positive association in heart failure, presumably reflecting the abnormal concurrence of increased atrial stretch and diminished renal perfusion in this condition. Plasma ANF values rise with increasing severity of heart failure and fall with effective treatment. 4. Plasma ANF values are elevated in hypertension and cardiac tachyarrhythmias possibly reflecting raised central venous and atrial pressures. 5. A variety of other disorders may be associated with abnormal plasma ANF values including cirrhosis and the syndrome of inappropriate ADH secretion. 6. Evidence from low-dose infusions of ANF in normal volunteers suggests that the variations in plasma ANF seen in health and disease are sufficient to exert biological effects. 7. The advent of a specific antagonist is needed to provide further insight into the physiological and pathophysiological roles of ANF.

Effects of Atrial Natriuretic Factor on Natriuresis and cGMP in Patients with Essential Hypertension

Human atrial natriuretic factor (h-ANF) or its vehicle only, were infused at rates of 0.8, 1.6 and 3.2 micrograms/min over three successive 30-min periods, into five patients with mild essential hypertension and seven normotensive controls. Baseline (mean +/- s.e.m.) plasma ANF levels were 13 +/- 2 in patients and 8 +/- 1 pg/ml in controls. During the first period, plasma ANF and cyclic guanosine monophosphate (cGMP) levels increased in both groups without significant alteration of blood pressure, heart rate, diuresis, natriuresis or cGMP excretion rate. During the second period of infusion, plasma ANF levels increased up to 179 +/- 39 and 177 +/- 30 pg/ml in patients and controls and plasma cGMP concentrations increased X 5.0 and X 4.9, respectively; natriuresis increased X 2.4 in patients and X 3.1 in controls while urinary cGMP increased X 10.9 in patients and X 10.5 in controls. During the last period, three controls became hypotensive while blood pressure remained stable in the other controls and in the patients with essential hypertension. During this period, the increases in plasma ANF concentration, diuresis, natriuresis and urinary cGMP excretion were similar in both groups. However, the mean plasma cGMP concentration after 90 min infusion was significantly higher in hypertensive patients than in control subjects (30.7 +/- 3.3 versus 15.6 +/- 3.4 pmol/ml, P less than 0.05). The half-life and clearance of plasma ANF, upon discontinuation of the infusion, were similar in both groups. Our data suggest that patients with mild essential hypertension have enhanced increases in plasma cGMP but normal increases in diuresis, natriuresis and cGMP excretion following infusion of h-ANF at pharmacological rates.

Mechanisms of release of atrial natriuretic factor. II. Effect of chronic administration of α- and β-adrenergic and cholinergic agonists on plasma and atrial ANF in the rat

The effect that chronic subcutaneous infusion of α- and β-adrenergic and cholinergic agonists on plasma and atrial ANF was investigated. Isoproterenol, a β-adrenergic agonist, and carbachol, a cholinergic agonist produced a 3-fold increase in plasma ANF levels which were constant until the end of the infusion period. An increased natriuresis was observed in the same groups which was positively correlated with plasma ANF. No differences were observed in atrial content of ANF between the experimental groups. A sharp post-surgery decline in plasma ANF was observed in control, phenylephrine and epinephrine-treated groups which was maintained during the observation period of five days. This suggests that the rise in plasma ANF induced by isoproterenol and carbachol may be secondary to hemodynamic changes and not to direct receptor stimulation, and may play a role in the observed natriuresis. It is also suggested that the depression of plasma ANF may contribute to the well known post-surgery sodium retention.

Increased plasma ANF levels and cardiac filling pressure after acute β-blockade in conscious hypertensive rats

Increased plasma ANF levels and cardiac filling pressure after acute β-blockade in conscious hypertensive rats