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.

Glomerular atrial natriuretic factor receptors in experimental congestive heart failure

1993 ◽  
Vol 265 (3) ◽  
pp. H923-H928 ◽  
Author(s):  
R. Isnard ◽  
A. Carayon ◽  
J. Eurin ◽  
G. Maistre ◽  
N. Bouanani ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Atrial Natriuretic Factor ◽  
Renal Response ◽  
Cgmp Production ◽  
Natriuretic Factor ◽  
Abdominal Aortic ◽  
Atrial Natriuretic

Heart failure is usually characterized by a relative insensitivity to atrial natriuretic factor (ANF). Downregulation of ANF receptors has been reported but remains controversial. Renal response to ANF infusion, glomerular ANF receptors, and guanosine 3',5'-cyclic monophosphate (cGMP) production have been studied in rabbits with congestive heart failure (CHF) after traumatic aortic regurgitation and abdominal aortic stenosis. Diuresis and natriuresis induced by ANF infusions were significantly decreased in CHF animals. Plasma cGMP was higher in CHF rabbits before ANF administration than in controls (37.6 +/- 7.2 vs. 17.1 +/- 3.9 pmol/ml, P < 0.02) and increased to a same level after ANF in both groups (48.8 +/- 4.2 vs. 52.5 +/- 2.8 pmol/ml, NS). No difference was found in glomerular ANF receptor density (436 +/- 54 vs. 425 +/- 57 fmol/mg protein, NS) nor in affinity between the two groups (dissociation constant; 240 +/- 24 vs. 347 +/- 49 pM, NS). Moreover, in vitro glomerular cGMP production in response to exogenous ANF was preserved. In conclusion, despite a blunted renal response to ANF in vivo, glomerular ANF receptors were unchanged in this model, and no defect in cGMP production in response to ANF was found. This suggests the existence of an intracellular defect beyond the second messenger.

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.

Interaction of amiloride and hydrochlorothiazide with atrial natriuretic factor in the medullary collecting duct

1988 ◽  
Vol 66 (5) ◽  
pp. 648-654 ◽  
Author(s):  
Douglas R. Wilson ◽  
U. Honrath ◽  
H. Sonnenberg
Keyword(s):  
Atrial Natriuretic Factor ◽  
Collecting Duct ◽  
Sodium Reabsorption ◽  
Second Phase ◽  
Potassium Excretion ◽  
Additive Effects ◽  
Natriuretic Factor ◽  
Medullary Collecting Duct ◽  
Atrial Natriuretic

Medullary collecting duct function was studied using the in vivo microcatheterization technique in three groups of rats receiving amiloride, hydrochlorothiazide, or both diuretics. In each group of animals, atrial natriuretic factor (ANF 99–126) was given in the second phase of the experiment. The combination of amiloride and hydrochlorothiazide resulted in a more marked natriuresis than either diuretic given as a single agent. Sodium reabsorption in the medullary collecting duct, as a fraction of the delivered load, was reduced from 64% (amiloride) and 69% (hydrochlorothiazide) to 29% (amiloride and hydrochlorothiazide). Atrial natriuretic factor reduced collecting duct sodium reabsorption when added to amiloride or hydrochlorothiazide to 23% and to 41%, respectively, but had no additional effect when given with amiloride and hydrochlorothiazide. Potassium excretion with amiloride and hydrochlorothiazide was intermediate between amiloride or hydrochlorothiazide given as single agents. With the diuretic combination, potassium transport showed no significant reabsorption or secretion along the medullary collecting duct, amiloride was associated with potassium reabsorption, and hydrochlorothiazide was associated with potassium secretion in the duct. The results confirm the importance of the medullary collecting duct as a site of diuretic action. The known additive effects of amiloride and hydrochlorothiazide on sodium excretion and the opposing effects of these agents on potassium excretion occur, to a major degree, in the medullary collecting duct. Furthermore, the additive effects of amiloride and ANF indicate that blocking of amiloride-sensitive sodium channels is not the only mechanism of action of ANF on duct salt transport in vivo.

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

scholarly journals Collecting Duct Is a Site of Sodium Retention in PAN Nephrosis: A Rationale for Amiloride Therapy

2001 ◽  
Vol 12 (3) ◽  
pp. 598-601 ◽  
Author(s):  
GEORGES DESCHÊNES ◽  
MONIKA WITTNER ◽  
ANTONIO DI STEFANO ◽  
SYLVIE JOUNIER ◽  
ALAIN DOUCET
Keyword(s):  
Collecting Duct ◽  
Urinary Sodium Excretion ◽  
Sodium Balance ◽  
Sodium Reabsorption ◽  
Puromycin Aminonucleoside ◽  
Aldosterone Receptor ◽  
Collecting Tubules ◽  
A Site

Abstract. Micropuncture studies of the distal nephron and measurements of Na,K-ATPase activity in microdissected collecting tubules have suggested that renal retention of sodium in puromycin aminonucleoside (PAN) nephrotic rats originates in the collecting duct. The present study demonstrated this hypothesis by in vitro microperfusion and showed that amiloride was able to restore sodium balance. Indeed, isolated perfused cortical collecting ducts from PAN-treated rats exhibited an abnormally high transepithelial sodium reabsorption that was abolished by amiloride, and in vivo administration of amiloride fully prevented decreased urinary sodium excretion and positive sodium balance in nephrotic rats. As expected from the aldosterone independence of Na+ retention in PAN nephrotic rats, blockade of aldosterone receptor by potassium canrenoate did not alter urinary Na+ excretion, Na+ balance, or ascites formation in PAN nephrotic rats.

Atrial natriuretic factor counteracts sodium-retaining actions of insulin in normal men

1993 ◽  
Vol 265 (3) ◽  
pp. R584-R590 ◽  
Author(s):  
J. A. Miller ◽  
S. Abouchacra ◽  
B. Zinman ◽  
K. L. Skorecki ◽  
A. G. Logan
Keyword(s):  
Sodium Excretion ◽  
Atrial Natriuretic Factor ◽  
Low Dose ◽  
Diastolic Pressure ◽  
Sodium Reabsorption ◽  
Acute Administration ◽  
Sodium Retention ◽  
Natriuretic Factor ◽  
Normal Men ◽  
Atrial Natriuretic

It has been hypothesized that hyperinsulinemia is causally related to hypertension by its effect on renal sodium transport. To examine the relationship between the sodium-retaining actions of insulin and atrial natriuretic factor (ANF), 16 healthy subjects were studied on three occasions, approximately 1 wk apart, using standard clearance techniques to evaluate responses during the acute administration of insulin, low-dose ANF, or both. In study 1, the euglycemic clamp was used to increase plasma insulin 10-fold to an average of 320 +/- 14 (SE) pM. This maneuver produced an immediate and persistent fall in sodium excretion from 0.315 +/- 0.02 to 0.207 +/- 0.02 mmol/min (P < 0.001) independent of change in renal hemodynamics, lithium clearance, and catecholamines. The decline in sodium excretion was associated with a marked increase in fractional distal sodium reabsorption. Systolic and diastolic pressure did not change significantly. In study 2, low-dose ANF (0.3 pmol.kg-1.min-1) designed to raise plasma levels to twice baseline was administered simultaneously in a repeat of study 1. This maneuver abolished insulin-mediated sodium reabsorption. In study 3, low-dose ANF infusion alone produced no changes in tubular handling of sodium. Our findings indicate that insulin at levels found in hyperinsulinemic states caused sodium retention and that physiological increases in plasma ANF concentration abolished the sodium-retaining action of insulin. Our findings suggest that if hypertension is causally related to hyperinsulinemia, mechanisms besides renal sodium retention are responsible for the hypertensive properties of insulin.

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.

Sign in / Sign up

Export Citation Format

Share Document