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Studies were done in male cardiomyopathic and normal hamsters to examine the effect of heart failure on atrial natriuretic factor (ANF) secretion. Five groups of animals were studied. The hamsters were 70, 150, 200, 250 and 300 days old. The degree of heart failure became more severe with age. This was associated with a marked increase in left and right atrial weight. Plasma ANF rose in the cardiomyopathic hamsters with age, and no significant change was seen in the normal animals. ANF levels in the atrial tissue declined as the animals developed heart failure, suggesting that ANF release increased in heart failure. To examine these directly, the right and left atria of these animals were isolated and superfused in a modified Langendorff apparatus. The effluents from these experiments were collected and analyzed for ANF levels. Analysis showed that ANF secretion (expressed as pg/min/mg of tissue) declined in heart failure. Since there were significant atrial hypertrophy, the results were also expressed as picogram per minute per atrium. When the data were shown as picogram per minute per atrium, there was a marked increase in ANF secretion. The present data show that one of the factors causing an increase in circulating ANF in heart failure is augmented secretion.

Magnesium is the second most abundant divalent ion in the body, but the effects of this cation on atrial natriuretic peptide (ANP) release have not been examined. The present study was conducted to determine the effect of magnesium on ANP secretion. Experiments were conducted in six groups of male Wistar rats. Each group was assigned a diet containing a different amount of magnesium. Plasma magnesium was 0.42 +/- 0.01, 0.63 +/- 0.01, 0.75 +/- 0.02, 0.97 +/- 0.03, 1.03 +/- 0.01, and 1.19 +/- 0.01 mM in groups I, II, III, IV, V, and VI, respectively. Plasma ANP concentration was significantly higher in the hypermagnesemic animals and significantly lower in the hypomagnesemic rats. A significant positive correlation was found between plasma magnesium and plasma ANP levels (y = 88 + 23 chi; r = 0.46; P less than 0.01). ANP concentration in the atria was lower in hypomagnesemic rats and higher in hypermagnesemic rats. This suggests that the low concentrations of ANP found in the plasma of hypomagnesemic animals were due to the lack of ANP in the atria. The atria from the various groups were isolated and perfused in a modified Langendorff apparatus to measure the rate of ANP secretion. Our results showed that the hypomagnesemic rats have a lower release rate as opposed to that seen in hypermagnesemic animals. A significant correlation was also seen between ANP secretion and tissue ANP concentration. The higher rate of ANP release from the heart of hypermagnesemic animals was due to the presence of more ANP, which was reduced during hypomagnesemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Previous studies have shown that acute calcium load causes an increase in circulating plasma atrial natriuretic factor (ANF) levels. The present study was conducted to examine the effect of high dietary calcium on ANF release. Experiments were performed on two groups of male Wistar rats. Hypercalcemic (n = 12) and normocalcemic (n = 12) animals were placed on a high and normal calcium diet, respectively, for 14 days before study. A 24-hour renal clearance was conducted on all animals before superfusion studies. Clearance results showed that high dietary calcium induced a significant increase in plasma calcium (2.69 +/- 0.02 v 2.90 +/- 0.77 mmol/L; P less than .01). This elevation is plasma calcium was associated with a marked increase in calcium excretion (fractional excretion of calcium, 1.91% +/- 0.33% v 8.17% +/- 0.11%, and was correlated with a significant increase in plasma ANF levels (97 +/- 6 v 167 +/- 20 pg/mL). We also measured immunoreactive ANF in the atria of hypercalcemic and normocalcemic rats. ANF content and concentration in the atria were lower in hypercalcemic (465 +/- 36 ng/mg) than in normocalcemic rats (635 +/- 30 ng/mg). This implies that ANF secretion is stimulated by hypercalcemia. To examine this directly, the right atrium from hypercalcemic and normocalcemic rats was superfused in a modified Langendorff preparation. Spontaneous release of ANF from the isolated right atria of hypercalcemic animals (19 +/- 0.8 pg/min/mg) was significantly higher (P less than .01) than from the normocalcemic rats (8.6 +/- 0.3 pg/min/mg). These results suggest that elevation of plasma ANF levels in hypercalcemia is due to an increase in ANF secretion.

Background: This study evaluated the role of changes in heart rate, atrial pressure, volume, and cardiac tissue atrial natriuretic factor (ANF) concentration in the modulation of plasma ANF concentration in a model of pacing-induced heart failure., Methods and Results: The effects of acute right ventricular pacing (250 beats/min), acute volume expansion (35 ml/min), and volume expansion after 1 week of right ventricular pacing on plasma ANF concentration were compared in eight dogs (group 1). As shown during right ventricular pacing previously, volume expansion produced significant increases in cardiac filling pressures and left atrial volume. Right ventricular pacing and volume expansion produced similar increments in plasma ANF concentration: from 32 +/- 12 to 168 +/- 153 pg/ml (p less than 0.05) and from 32 +/- 9 to 137 +/- 113 pg/ml (p less than 0.05), respectively. When pacing was initiated after volume expansion, plasma ANF concentration increased further to 462 +/- 295 pg/ml (p less than 0.05) despite little change in filling pressures and left atrial volume. With repeated volume expansion after 1 week of pacing, there were no significant further increases in left atrial volume and plasma ANF concentrations (from 332 +/- 121 to 407 +/- 113 pg/ml) despite significant increases in filling pressures. Atrial and ventricular tissue samples were also obtained from 21 dogs paced to severe heart failure (group 2) and from 14 normal dogs (controls). In all groups, atrial ANF was higher than ventricular ANF concentration. At 1 week (group 1), left atrial appendage ANF concentration (6.2 +/- 2.5 versus 16.1 +/- 10.3 ng/mg) was reduced, whereas left ventricular free wall ANF concentration (0.62 +/- 0.31 versus 0.24 +/- 0.16 pg/mg) was increased compared with that of controls (both p less than 0.001). At severe heart failure (group 2), atrial ANF remained low, whereas ventricular ANF concentration was similar to that of the controls., Conclusions: These data indicate that in pacing-induced heart failure, changes in heart rate, atrial pressure, and volume all contribute to the increased plasma ANF concentration. However, by 1 week (early heart failure), ANF release is attenuated, perhaps because of the inability of the atria to be stretched further and because of reduced atrial ANF concentration. In addition, the ventricle may be an additional source of ANF.

The role of intracellular signals in the regulation of atrial natriuretic peptide (ANP) release was studied using the isolated left and right atria from a rat. The atria were perfused with Tyrode's solution, equilibrated with 95% O2-5% CO2 at 37 degrees C with a constant flow of 0.5 ml/min. Addition of epinephrine (10(-6) M), an alpha- and beta-agonist, to the perfusate induced the biphasic release of ANP from the right atrium without effect on the left. The initial peak (19.2 +/- 2.6 pg.min-1.ml-1) occurs 2-4 min after the administration of epinephrine, which lasted 4-6 min and returned to base line (10.4 +/- 1.1 pg.min-1.mg-1). The second peak (16.5 +/- 2.0 pg.min-1.ml-1) appeared 30-35 min after epinephrine administration and was sustained for 100 min, at which time the experiment was terminated. The first peak was stimulated by isoproterenol (10(-6) M), a beta-agonist, and blunted by propranolol (10(-6) M), a beta-antagonist. The second peak appeared following methoxamine (10(-6) M), an alpha-agonist, and could be suppressed by phentolamine (10(-6) M), an alpha-antagonist. These studies indirectly suggest that the adenosine 3',5'-cyclic monophosphate system and the inositol triphosphate system are involved in ANP secretion, with the former responsible for the initial rapid release and the latter maintaining the secretion.

Experiments were conducted to examine the release of atrial natriuretic peptide (ANP) in an isolated atrium in the presence and absence of sinus node tissue. The first series of experiments were conducted with the aid of a metabolic chamber to examine the spontaneous release of ANP by the right atrium with and without the sinus node region. The left atrium was also studied. The right atrium with the sinus node, quiescent right atrium without the sinus node, and the left atrium were incubated at 35 degrees C in 10 mL of oxygenated Tyrode's solution. After 40 min of equilibration, the incubation medium was removed at 10-min intervals for the determination of immunoreactive ANP concentration. The right atria with the sinus node released the highest amount of ANP into the incubation medium (32.2 +/- 2.7 pg.min-1.mg-1), compared with quiescent right atria (20.9 +/- 3.7 pg.min-1.mg-1). The left atria released the least amount of ANP into the incubation medium (9.9 +/- 1.5 pg.min-1.mg-1) when compared with the quiescent right atria and the right atria. In the second series of experiments, the right atrium was divided into the sinus node region and the quiescent right atrium, and these tissues were studied in paired fashion with a modified Langendorff preparation. The right atrium without the sinus node and sinus node region were perfused with Tyrode's solution, equilibrated with 95% O2 and 5% CO2 at 37 degrees C with a constant flow of 0.5 mL/min.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of thyroid hormone on circulating levels of atrial natriuretic peptide (ANP) was studied in experimental hyperthyroid and hypothyroid rats. Plasma ANP was 102 +/- 5 pg/ml in euthyroid rats, 82 +/- 4 pg/ml in hypothyroid rats, and 138 +/- 11 pg/ml in hyperthyroid rats. We have also measured immunoreactive ANP in the atria of euthyroid, hypothyroid, and hyperthyroid rats. ANP content and concentration in the atria were lower (546 +/- 32 pg/mg tissue) in hyperthyroid rats than in hypothyroid rats (802 +/- 74 pg/mg tissue). Right atrium from euthyroid, hypothyroid, and hyperthyroid rats was superfused with a modified Langendorff preparation. Spontaneous release of ANP was significantly higher from the hyperthyroid rats (20 +/- 2 pg.min-1.mg-1) than from the hypothyroid rats (5.6 +/- 0.5 pg.min-1.mg-1). ANP release from the euthyroid rats was 9.3 +/- 1.2 pg.min-1.mg-1. These results indicate hyperthyroidism causes an increase in ANP secretion and a decreased release occurs during hypothyroidism.

A sensitive radioimmunoassay for atrial natriuretic peptide was used to examine the relation between circulating atrial natriuretic peptide and cardiac filling pressure in normal human subjects, in patients with cardiovascular disease and normal cardiac filling pressure, and in patients with cardiovascular disease and elevated cardiac filling pressure with and without congestive heart failure. The present studies establish a normal range for atrial natriuretic peptide in normal human subjects. These studies also establish that elevated cardiac filling pressure is associated with increased circulating concentrations of atrial natriuretic peptide and that congestive heart failure is not characterized by a deficiency in atrial natriuretic peptide, but with its elevation.

The elevation of cardiac filling pressure induces the release of atrial natriuretic peptide into the circulation. Ischemia during exercise in patients with coronary artery disease may manifest itself with elevation of cardiac filling pressure before the onset of electrocardiographic changes or chest pain. Thus, patients with ischemic heart disease might have an elevated circulating atrial natriuretic peptide after exercise. The present study investigated the effect of exercise on circulating atrial natriuretic peptide in patients with and without ischemic heart diseases. Group 1 was composed of five patients who had ischemic heart disease by clinical history, previous myocardial infarction, angina or angiographically proven coronary artery disease and positive electrocardiogram during exercise. Group 2 was composed of five patients without ischemic heart disease and negative electrocardiogram response. Heart rate, blood pressure, and atrial natriuretic peptide were measured during routine treadmill exercise testing using the Bruce protocol. Our results indicate that the rate of rise of heart rate (12.3 +/- 1.8 vs. 8.5 +/- 0.7 beats/min/min), blood pressure (7.1 +/- 1 vs. 4.2 +/- 0.8 mm Hg/minute), and atrial natriuretic peptide (4.1 +/- 1 vs. 1.4 +/- 0.3 pg/ml/min) was significantly elevated in patients with ischemic heart disease compared to the group 2 patients. These findings suggest that the disproportionate elevation of atrial natriuretic peptide after exercise in ischemia may be caused by elevation of cardiac filling pressure, which may provide a noninvasive method for the diagnosis of ischemic heart disease.