Inactivation of atrial natriuretic factor in blood

1985 ◽  
Vol 63 (12) ◽  
pp. 1615-1617 ◽  
Author(s):  
Anthony T. Veress ◽  
Chee K. Chong ◽  
Harald Sonnenberg
Keyword(s):  
Rat Heart ◽  
Atrial Natriuretic Factor ◽  
Physiological Role ◽  
White Cell ◽  
Tissue Extracts ◽  
Natriuretic Factor ◽  
Blood Elements ◽  
Heart Atria ◽  
Atrial Natriuretic

Tissue extracts of rat heart atria contain a family of peptides with natriuretic and vasorelaxant properties. It has been shown by others that inactivation of this atrial natriuretic factor may involve endogenous peptidases. The present experiments demonstrate that incubation in blood in vitro reduces the natriuretic activity of the factor. Specifically, inactivation was associated with a white cell/platelet fraction, indicating that these blood elements may play a physiological role in the metabolism of this new putative hormone.

Homologous IRCM-Serine Protease 1 from pituitary, heart atrium and ventricle: A common pro-hormone maturation enzyme?

1986 ◽  
Vol 6 (9) ◽  
pp. 835-844 ◽  
Author(s):  
Nabil G. Seidah ◽  
James A. Cromlish ◽  
Josée Hamelin ◽  
Gaétan Thibault ◽  
Michel Chrétien
Keyword(s):  
Serine Protease ◽  
Rat Heart ◽  
Atrial Natriuretic Factor ◽  
Cleavage Sites ◽  
Heart Atrium ◽  
Natriuretic Factor ◽  
Heart Atria ◽  
Atrial Natriuretic

IRCM-Serine Protease 1 (IRCM-SP1) has recently been isolated and characterized from porcine pituitary anterior and neurointermediate lobes (Cromlish et al., 1986a, J. Biol. Chem.261:10850–10858; Cromlish et al., 1986b, J. Biol. Chem.261:10859–10870). This pituitary serine protease was shown to selectively cleave human proopiomelanocortin (POMC)-derived peptides at both pairs of basic residues and C-terminal to specific Arg residues, all known to be cleaved in vivo. Here, a similar enzyme was isolated from rat heart atria and ventricles. Rat IRCM-SP1 was shown to be highly specific for the same cleavage sites in POMC, as the porcine pituitary homologue. Furthermore, the rat and the porcine enzymes cleave rat pro-Atrial Natriuretic Factor (pro-ANF 1–126) to yield ANF 103–126, 102–126 and 99–126 in that order of preference. This suggests that in vitro the cleavage sites preferred in pro-ANF resemble those found in brain and hypothalamus. The enzyme is nine times more abundant in atria versus ventricles/mg protein. It is concluded that IRCM-SP1, could well represent a common pro-hormone maturation enzyme for POMC and Pro-ANF and possibly many other pro-hormones.

The physiology of atrial natriuretic factor

1987 ◽  
Vol 65 (10) ◽  
pp. 2021-2023 ◽  
Author(s):  
H. Sonnenberg
Keyword(s):  
Atrial Natriuretic Factor ◽  
Collecting Duct ◽  
Physiological Role ◽  
Sodium Balance ◽  
Sodium Reabsorption ◽  
Spontaneously Hypertensive ◽  
Renal Response ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

Following the discovery of the natriuretic effect of atrial extract, our laboratory attempted to dissect the possible physiological role of atrial natriuretic factor. Initial micropuncture experiments demonstrated that the reduction of tubular sodium reabsorption was localized in the medullary collecting duct, a nephron site in which sodium transport was known to be inhibited after acute hypervolemia. Partial removal of the endogenous source of atrial natriuretic factor was associated with a reduced renal response to hypervolemia, confirming that the factor is causally involved in acute sodium balance. In vitro incubation of atrial tissue was used to investigate mechanisms of release of atrial natriuretic factor. It was found that agonists known to activate the intracellular polyphosphoinositide system in other tissues were effective in releasing natriuretic activity from the atria into the incubation medium. To determine whether atrial natriuretic factor might play a role in hypertension, atrial natriuretic content was measured in spontaneously hypertensive rats and their normotensive controls. Hypertension was associated with increased content. Since the renal response to exogenous factor was not impaired in these animals, we suggested that the increased content might play a compensatory role. Our early studies thus indicated that atrial natriuretic factor was a previously unrecognized hormone involved in cardiovascular regulation.

Thirty years of research on atrial natriuretic factor: historical background and emerging concepts

2011 ◽  
Vol 89 (8) ◽  
pp. 527-531 ◽  
Author(s):  
Adolfo J. de Bold
Keyword(s):  
Atrial Natriuretic Factor ◽  
Hybrid Approach ◽  
Biological Properties ◽  
Historical Background ◽  
Endocrine Function ◽  
Intracellular Targeting ◽  
Natriuretic Factor ◽  
Polypeptide Hormones ◽  
Atrial Natriuretic

The discovery of the natriuretic properties of atrial muscle extracts pointed to the existence of an endocrine function of the heart that is now known to be mediated by the polypeptide hormones atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP). On the basis of such a finding, approximately 27 000 publications to date have described a wide variety of biological properties of the heart hormones as well as their application as therapeutic agents and biomarkers of cardiac disease. Stimulation of secretion of ANF and BNP from the atria is mediated through mechanisms involving G proteins of the Gq or Go types. We showed that the latter type underlies the transduction of muscle stretch into stimulated secretion and that it is more highly abundant in atria than in ventricles. The Gαo-1 subunit appears to play a key role in the biogenesis of atrial granules and in the intracellular targeting of their contents. Protein interaction studies using a yeast two-hybrid approach showed interactions between Gαo-1, proANF, and the intermediate conductance, calcium-activated K+ channel SK4. Pharmacological inhibition of this channel decreases ANF secretion. Unpublished studies using in vitro knockdowns suggest interdependency in granule protein expression levels. These studies suggest previously unknown mechanisms of intracellular targeting and secretion control of the heart hormones that may find an application in the therapeutic manipulation of circulating ANF and BNP.

The Action of Atrial Natriuretic Factor on Glomerular Diameter in Vitro

1988 ◽  
Vol 529 (1 Fourth Colloq) ◽  
pp. 175-177
Author(s):  
WARREN L. ROSENBERG ◽  
CHRISTOPHER V. KEOGH ◽  
BEVERLY A. HALL ◽  
LUIGI ALBANO
Keyword(s):  
Atrial Natriuretic Factor ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

Control of atrial natriuretic factor release from a rat heart-lung preparation

1987 ◽  
Vol 252 (3) ◽  
pp. R498-R502 ◽  
Author(s):  
J. R. Dietz
Keyword(s):  
Rat Heart ◽  
Atrial Natriuretic Factor ◽  
Venous Return ◽  
Sodium Concentration ◽  
Aortic Pressure ◽  
Plasma Sodium ◽  
Natriuretic Factor ◽  
Time Period ◽  
Lung Preparation ◽  
Atrial Natriuretic

These experiments examined the effects of altering venous return, aortic pressure, or perfusate sodium concentration on the release of atrial natriuretic factor (ANF) from a rat heart-lung preparation. Changes in perfusate ANF concentration during each time period (delta ANF) were used as an index of ANF secretion. Raising the height of the venous return reservoir from 2-3 to 5-7 cm above the heart increased delta ANF from 88 +/- 19 to 748 +/- 154 pg X ml-1 X 10 min-1 (P less than 0.01, n = 7). In control experiments where the height of the reservoir was not increased, delta ANF was unchanged (65 +/- 35 vs. 43 +/- 26 pg X ml-1 X 10 min-1, n = 6). Increasing aortic pressure from 60 to 100 mmHg increased ANF from 43 +/- 10 to 107 +/- 20 pg X ml-1 X 15 min-1 (P less than 0.05, n = 6). Separate groups of heart-lung preparations were perfused with solutions with sodium concentrations of 132 +/- 1, 144 +/- 2, or 166 +/- 1 meq/l (n = 8/group). delta ANF was 45 +/- 14, 50 +/- 17, and 52 +/- 22 pg X ml-1 X 10 min-1, respectively. These values were not significantly different. These results suggest that ANF plays a role in the control of blood volume and blood pressure but do not support a role for ANF in the control of plasma sodium concentration.

Effect of hypoxia on atrial natriuretic factor and aldosterone regulation in humans

1990 ◽  
Vol 258 (2) ◽  
pp. E243-E248 ◽  
Author(s):  
D. L. Lawrence ◽  
J. B. Skatrud ◽  
Y. Shenker
Keyword(s):  
Atrial Natriuretic Factor ◽  
Acute Hypoxia ◽  
Physiological Role ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Natriuretic Factor ◽  
Hemoglobin Saturation ◽  
Atrial Natriuretic

To evaluate the possible physiological role of atrial natriuretic factor (ANF) on the observed dissociation of aldosterone from the renin-angiotensin system during acute hypoxia, 7 men, ages 18-27 yr, were studied on two separate days for 1 h under hypoxic (12% O2) and normoxic (room air) conditions. Subjects were on a low-salt diet (urinary sodium 67 +/- 13 meq/24 h) and suppressed with dexamethasone. Hemoglobin saturation decreased during hypoxemia to 68 +/- 1% (P less than 0.01), whereas heart rate increased from 65 +/- 3 to 89 +/- 5 beats/min (P less than 0.01). Plasma aldosterone levels decreased 43% from basal during hypoxemia (P less than 0.01), whereas ANF levels increased by 50% (P less than 0.05). Levels of both were unchanged during normoxemia. Plasma renin activity, angiotensin II, blood pressure, and pH did not change under either condition, and plasma cortisol levels were totally suppressed. These results indicate that acute hypoxemia is a potent stimulus for ANF release and that ANF is probably a major factor responsible for the dissociation of aldosterone from the renin-angiotensin system under these conditions.

Atrial natriuretic factor binding sites in the jejunum

1989 ◽  
Vol 256 (2) ◽  
pp. G436-G441 ◽  
Author(s):  
C. Bianchi ◽  
G. Thibault ◽  
A. De Lean ◽  
J. Genest ◽  
M. Cantin
Keyword(s):  
Binding Sites ◽  
Atrial Natriuretic Factor ◽  
Specific Binding ◽  
Rat Tissues ◽  
Rat Jejunum ◽  
Specific Binding Sites ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

We have studied the localization and the characterization of atrial natriuretic factor (ANF) binding sites by radioautographic techniques. Quantitative in vitro radioautography with a computerized microdensitometer demonstrated the presence of high-affinity, low-capacity 125I-ANF-(99-126) binding sites (Kd, 48 pM; Bmax, 63 fmol/mg protein) mainly in the villi of 20-microns slide-mounted transverse sections of the rat jejunum. Competition curves showed 50% inhibitory concentrations of 55 and 1,560 pM for ANF-(99-126) and ANF-(103-123), respectively. In vivo electron microscope radioautography showed that 80% of the silver grains were localized on the lamina propria fibroblast-like cells, 18% on mature enterocytes, and 2% on capillaries. Bradykinin and adrenocorticotropin did not compete with ANF binding. These results demonstrate that ANF binding sites in the rat jejunum possess the pharmacological characteristics of functional ANF receptors encountered in other rat tissues, and ultrastructural radioautographs show their cellular distribution. Taken together, these results demonstrate the presence and the localization of specific binding sites for ANF in the jejunal villi of the rat small intestine.

Identification of the Released form of Atrial Natriuretic Factor by the Perfused Rat Heart

1986 ◽  
Vol 182 (1) ◽  
pp. 137-141 ◽  
Author(s):  
G. Thibault ◽  
R. Garcia ◽  
J. Gutkowska ◽  
C. Lazure ◽  
N. G. Seidah ◽  
...  
Keyword(s):  
Rat Heart ◽  
Atrial Natriuretic Factor ◽  
Perfused Rat Heart ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

In vitro secretion of atrial natriuretic factor: receptor-mediated release of prohormone

1988 ◽  
Vol 254 (5) ◽  
pp. R809-R814 ◽  
Author(s):  
A. T. Veress ◽  
S. Milojevic ◽  
C. Yip ◽  
T. G. Flynn ◽  
H. Sonnenberg
Keyword(s):  
Atrial Natriuretic Factor ◽  
Active Form ◽  
High Concentration ◽  
Natriuretic Factor ◽  
Rat Hearts ◽  
Agonist Concentration ◽  
Atrial Natriuretic Factor Receptor ◽  
Atrial Natriuretic

Secretion of atrial natriuretic factor (ANF) in vivo is thought to be mediated by atrial distension. We have shown previously that nonstretched atria can release natriuretic activity in vitro when stimulated by certain agonists. In the present study atrial appendages from freshly excised rat hearts were incubated at 37 degrees C for up to 1 h in the presence of either vasopressin (5 X 10(-9) mol/l) or angiotensin II (2.5 X 10(-7) mol/l). Aliquots of postincubation media were injected intravenously into anesthetized bioassay rats to determine natriuretic activity. Control media, in which atria had been incubated without agonist, did not cause natriuresis. Significant increases in sodium excretion were seen after injection of media in which atria had been incubated in the presence of either agonist. Injection of medium with the same agonist concentration did not result in comparable natriuresis. Radioimmunoassay (RIA) indicated a high concentration of immunoactive ANF in the natriuretic media. However, radioreceptor assay (RRA) of the same media gave apparent ANF concentrations that were lower by about three orders of magnitude. Because the antibody used in the RIA cross reacts with ANF prohormone, whereas the RRA is sensitive only to the active form, we concluded that agonist-induced, stretch-independent release of ANF is in the form of prohormone, which can be converted to the active hormone in the circulation of the bioassay animal. The conclusion of prohormone release was confirmed by liquid chromatography. The data thus suggest that receptor-mediated as well as stretch-induced ANF secretion may be important in regulating the activity of the ANF system.

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