Atrial natriuretic factor

Mammalian atria contain different peptides with potent diuretic, natriuretic, smooth muscle relaxing and blood pressure lowering properties. A preprohormone of these peptides is synthetized and stored in specific granules in atrial myocytes. Different peptides have been isolated, analyzed and in vitro synthetized. Their biological activity indicates a potential role in the regulation of volume and sodium homeostasis as well as in blood pressure regulation.     

Atrial natriuretic peptide--cyclic GMP coupling and urinary sodium excretion during acute volume expansion in man

The present study examines hormonal and renal responses to acute volume expansion in normal man, with particular emphasis on the atrial natriuretic peptide (ANP)--cyclic GMP coupling. Two liters of isotonic saline were infused into eight normotensive male subjects over a 1-h period. Plasma and urinary measurements were made before, during, and up to 300 min after the start of the saline infusion. With the initial increase in urinary sodium excretion there were increases in plasma ANP and plasma cyclic GMP, which reached maximum levels at 15 min after the end of the saline infusion. Urinary cyclic GMP increased gradually during saline infusion up to approximately 60 min after the end of the infusion. Plasma ANP and plasma and urinary cyclic GMP excretion gradually declined thereafter. By contrast, urinary sodium excretion remained elevated up to the end of the observation period. The saline infusion was associated with marked reductions in plasma renin activity and aldosterone, which persisted up to the end of the study. These results suggest a coupling between the increases in plasma ANP, the production of cyclic GMP, and urinary sodium excretion, in particular during the initial renal response to acute volume expansion. However, other mechanisms including the suppression of the renin--angiotensin--aldosterone system may become increasingly important in the later natriuretic response to acute volume expansion.     

Atrial natriuretic factor in human plasma

A reproducible and sensitive radioimmunoassay (RIA) was developed to measure ANF in human plasma. Immunoreactive ANF was extracted from plasma with Sep-Pak cartridges, using 0.2% ammonium acetate (pH 4) with acetonitrile. The sensitivity of the assay was 3.9 pg/ml. The coefficient of variance for inter-assay and intra-assay was 16.8% and 6.8%, respectively. In normal healthy subjects (n = 67), ANF content was 11.9 +/- 1.3 pg/ml (mean +/- SEM). Significantly-higher ANF concentrations were found in proximal coronary sinus blood, being 6 to 37 times greater than in the peripheral circulation. Comparison of the prior extraction method with direct RIA revealed a good correlation (r = 91) in samples containing higher than 100 pg/ml ANF. No correlation was observed with lower values. The elution profiles of reverse-phase HPLC of peripheral and coronary sinus plasma extracts were similar but somewhat complex, with the main immunoreactive peak corresponding to a low-molecular-weight peptide.     

Atrial natriuretic factor in essential hypertension

We measured circulating levels of immunoreactive atrial natriuretic factor (ANF) in 10 patients with untreated, uncomplicated mild to moderate essential hypertension and in 15 normotensive controls. ANF concentrations were significantly higher in the hypertensive group than in the control group (38.4 +/- 6.9 pg/ml versus 18.3 +/- 1.8 pg/ml, p less than 0.02). A positive correlation between ANF levels and systolic, diastolic and mean blood pressure was noted in the total study population (p less than 0.008, r = 0.52; p less than 0.005, r = 0.55; p less than 0.02, r = 0.46, respectively). Thus, plasma ANF concentrations are elevated in essential hypertension and may result from increased intraarterial pressure.     

Atrial natriuretic factor: an overview

Heart atrial muscle cells in mammals are differentiated for a contractile as well as a secretory function. Through the latter, the heart plays an endocrine role; it synthesizes, stores, and releases a group of peptides collectively referred to as atrial natriuretic factor (ANF). ANF has natriuretic and hypotensive properties as well as an inhibitory effect on aldosterone and renin secretion. Thus ANF intervenes in the short- and long-term regulation of water and electrolyte balance and blood pressure. It is expected that further research in this new field will provide fresh insights into the pathophysiology of several important clinical entities and in the development of new pharmaceutical products.     

Effects of atrial appendectomy on circulating atrial natriuretic factor during volume expansion in the rat

This study examined the changes in the circulating level of endogenous atrial natriuretic factor during diuresis and natriuresis produced by acute volume expansion in anesthetized rats with either bilateral atrial appendectomy (n = 9) or sham operation (n = 9). Following control measurements in the sham-operated rats, 1% body weight volume expansion with isotonic saline produced an increment in urinary sodium excretion of over 4 mueq/min (P less than 0.05) while urine volume increased by more than 20 microliter/min (P less than 0.05). These responses were associated with a significant increase in immunoreactive plasma atrial natriuretic factor from a baseline value of 82 +/- 10 pg/ml to a level of 120 +/- 14 pg/ml (P less than 0.05). In contrast, in the group of rats with bilateral atrial appendectomy an identical degree of volume expansion increased urinary sodium excretion and urine volume by only 0.61 mueq/min (P less than 0.05) and 3.07 microliter/min (P less than 0.05), respectively. In this group, immunoreactive plasma atrial natriuretic factor remained statistically unchanged from a control value of 70 +/- 12 pg/ml to a level of 82 +/- 16 pg/ml (P greater than 0.05). Comparison of the two groups indicates that the natriuresis, diuresis, and plasma atrial natriuretic factor levels during volume expansion were significantly reduced in the rats with bilateral atrial appendectomy. No differences in mean arterial pressure and heart rate were observed between the two groups. These data demonstrate that removal of both atrial appendages in the rat attenuated the release of atrial natriuretic factor during volume expansion; and this effect, in turn, was associated with a reduction in the natriuretic and diuretic responses.     

Atrial natriuretic factor and body water distribution

In the rat, the effects of an atrial natriuretic factor (ANF) (Rat, 8-33 Peninsula Lab) on body water distribution have been evaluated. The ANF administration to nephrectomized animals produced a decrease in plasma volume and a slight increase in haematocrit and in plasma albumin concentration. No modifications were observed in total and intracellular water. The fluid efflux from the capillaries appeared to be located in the interstitial space. These results suggest that ANF could regulate plasma volume and systemic blood pressure, concurrently with its other known effects.     

Atrial natriuretic factor inhibits adenylate cyclase activity

The synthetic atrial natriuretic factor (ANF) (8- 33AA ) inhibited adenylate cyclase activity in aorta washed particles, mesenteric artery, and renal artery homogenates in a concentration dependent manner with an apparent Ki between 0.1 to 1nM . The extent of inhibition of adenylate cyclase by ANF varied from tissue to tissue. The adenylate cyclase from mesenteric artery and renal artery was inhibited to a greater extent as compared to that from aorta. ANF was also able to inhibit the stimulatory effects of hormones on adenylate cyclase activity and of agents such as F- and forskolin which activate adenylate cyclase by receptor- independent mechanism. In addition, ANF showed an additive effect with the inhibitory response of angiotensin II on adenylate cyclase from rat aorta. These studies for the first time demonstrate that ANF is an inhibitor of adenylate cyclase of several systems.     

Atrial natriuretic factor is a circulating hormone

The radioimmunoassay of atrial natriuretic factor (ANF) has been applied for determination of immunoreactive ANF (IR-ANF) in rat plasma. Immunoreactive ANF has been extracted from rat plasma by immunoaffinity column on Sepharose-4B anti-ANF or by Vycor glass. The mean concentrations of IR-ANF in ether anesthetized rats were found to be 1.61 +/- 0.14 ng/ml in female and 1.25 +/- 0.21 ng/ml in male rats when extracted on Sepharose-4B anti-ANF, and 1.21 +/- 0.10 ng/ml in females and 1.02 +/- 0.11 ng/ml in males when extracted by Vycor glass. A close linear correlation has been observed between the plasma IR-ANF concentrations in aorta and jugular vein. The described results indicate that atrial cardiocytes secrete atrial natriuretic factor into plasma. The heart is, therefore, an endocrine organ.     

Atrial natriuretic factor stimulates luteal guanylate cyclase

Effect of a synthetic atrial natriuretic peptide, rat atriopeptin II (rAP-II) on the formation of cyclic nucleotides and progesterone production in Percoll-purified rat luteal cells was investigated. Incubation of luteal cells with varying concentrations of rAP-II resulted in a dose-related stimulation of intracellular cyclic GMP content; maximum stimulation being achieved with 10 nM rAP-II. The increase in cyclic GMP formation was extremely rapid and a 12-fold increase in the cyclic GMP content over basal level was attained within 5 min of incubation of the cells with 10 nM rAP-II. In the presence of phosphodiesterase inhibitor, 3-isobutyl-1-methyl-xanthine, both basal and rAP-II-stimulated levels of cyclic GMP were increased approximately 10 times, but the magnitude of stimulation remained similar in the presence or absence of the inhibitor. The atrial peptide at the concentration of 1-100 nM, however, had no effect on either basal or gonadotropin-stimulated progesterone production and cyclic AMP formation by the luteal cells. Furthermore, the increase in the level of cellular cyclic GMP content of rAP-II was demonstrated to result from a selective activation of particulate guanylate cyclase.     

Atrial natriuretic factor in taurine-treated normal and cardiomyopathic hamsters

Diuretic and natriuretic activities of atrial extracts from BIO 14.6 (cardiomyopathic) and F1B (normal) hamsters at 180 days of age were measured by rat bioassay. Both activities were lower in BIO 14.6 extracts. Because of the reported protective action of taurine in the cardiomyopathic hamster, we tested the effect of 0.1 M taurine drinking upon the activity of atrial extracts. Urine flow and Na+ excretion were increased in both BIO 14.6 and F1B; however, comparatively larger increases in BIO 14.6 taurine drinkers abolished strain differences that were observed in water drinkers. Taurine drinking BIO 14.6 hamsters exhibited an increased plasma sodium concentration. Drinking of 0.6% NaCl also produced an elevated plasma sodium concentration in BIO 14.6. Extracts from hamsters with increased salt intake had diuretic and natriuretic activities that were not different from those of water drinkers. These findings confirm that ANF activity is deficient in BIO 14.6 hamsters, and this suggests a role for taurine in its production, release, and/or activation.     

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)