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.

Atrial natriuretic factor inhibits sodium transport in medullary collecting duct

1986 ◽  
Vol 250 (6) ◽  
pp. F963-F966 ◽  
Author(s):  
H. Sonnenberg ◽  
U. Honrath ◽  
C. K. Chong ◽  
D. R. Wilson
Keyword(s):  
Sodium Transport ◽  
Intravenous Infusion ◽  
Atrial Natriuretic Factor ◽  
Collecting Duct ◽  
Inhibitory Effect ◽  
Sodium Permeability ◽  
Natriuretic Factor ◽  
Tubular Lumen ◽  
Medullary Collecting Duct ◽  
Atrial Natriuretic

Characteristics of sodium transport in the inner medullary collecting duct were determined in anesthetized rats before and during intravenous infusion of synthetic atrial natriuretic factor (atriopeptin II). Infusion of the factor was associated with increased sodium delivery and reduced fractional reabsorption in the duct. Increasing delivery to the same extent by KCl infusion had no effect on fractional reabsorption. The results demonstrate that atrial natriuretic factor has a specific inhibitory effect on net sodium transport in this part of the nephron. The mechanism of this inhibition may involve induction of sodium permeability and consequent backflux into the tubular lumen.

Renal response to atrial natriuretic factor in conscious dogs with caval constriction

1985 ◽  
Vol 248 (4) ◽  
pp. R495-R500 ◽  
Author(s):  
R. H. Freeman ◽  
J. O. Davis ◽  
R. C. Vari
Keyword(s):  
Creatinine Clearance ◽  
Sodium Excretion ◽  
Atrial Natriuretic Factor ◽  
Conscious Dogs ◽  
Sodium Reabsorption ◽  
Renal Tubules ◽  
Potassium Excretion ◽  
Plasma Aldosterone Concentration ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

Constriction of the thoracic inferior vena cava to decrease venous return and atrial filling markedly elevates plasma renin activity (PRA) and plasma aldosterone concentration (PAC) and produces chronic sodium retention and ascites in the dog. Infusion of a synthetic atrial natriuretic factor into conscious dogs with caval constriction and ascites at doses of 175 and 350 ng X kg-1 X min-1 for 30 min each produced striking increases (P less than 0.05) in creatinine clearance, diuresis, and kaliuresis but failed to increase urinary sodium excretion. Infusions of atrial natriuretic factor at these doses into conscious normal dogs, however, produced a striking increase in sodium excretion from 41 +/- 14 and 55 +/- 19 mu eq/min to 150 +/- 58 and 181 +/- 49 mu eq/min (P less than 0.05 for both values). Creatinine clearance and urine flow also increased in these normal dogs, but potassium excretion remained unchanged during the infusion periods. Atrial natriuretic factor produced parallel suppression (P less than 0.05) of the elevated levels of PRA and PAC in the caval dogs but failed to significantly decrease either PRA or PAC in the normal animals. Arterial pressure, heart rate, and PAH clearance were unchanged in both groups of dogs during infusion of atrial natriuretic factor. These results suggest that the pattern of renal electrolyte excretion elicited in response to the acute infusion of atrial natriuretic factor is dependent, at least partially, on the preexisting status of the renal tubules to facilitate sodium reabsorption and potassium excretion. The results also are consistent with the concept that atrial natriuretic factor might function to tonically inhibit the renin-angiotensin-aldosterone system.

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.

Effects of synthetic atrial natriuretic factor in the isolated perfused rat kidney

1985 ◽  
Vol 249 (4) ◽  
pp. F603-F609 ◽  
Author(s):  
R. D. Murray ◽  
S. Itoh ◽  
T. Inagami ◽  
K. Misono ◽  
S. Seto ◽  
...  
Keyword(s):  
Atrial Natriuretic Factor ◽  
Rat Kidney ◽  
Potassium Excretion ◽  
Water Excretion ◽  
Pass System ◽  
Natriuretic Factor ◽  
High Concentrations ◽  
Atrial Natriuretic

It is known that atrial extracts (AE) and synthetic atrial natriuretic factor (ANF) can increase glomerular filtration rate (GFR) and electrolyte and water excretion both in vivo and in vitro. It is not clear, however, if ANF-induced increases in filtered load (increased GFR) are required to produce natriuresis and diuresis. We perfused isolated rat kidneys with AE or synthetic ANF at constant pressure in a single-pass system. Extracts of atrial tissue (1 mg/ml) and high concentrations of ANF (31 and 61 ng/ml) significantly increased both GFR and electrolyte and water excretion. During continued infusion of ANF, GFR stabilized at increased levels, but sodium and water excretion continued to increase. After the termination of infusions, GFR and potassium excretion returned to control levels, but sodium and water excretion remained significantly elevated. Infusion of a low concentration of ANF (3 ng/ml) significantly increased sodium and water excretion without changing either GFR or potassium excretion. We conclude that increases in GFR are not a prerequisite for natriuresis and diuresis in response to ANF, but that increases in GFR can potentiate the response. Furthermore, our data suggest that ANF increases potassium excretion only if it increases GFR.

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.

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.

Attenuation of renal effects of atrial natriuretic factor during rat pregnancy

1995 ◽  
Vol 268 (3) ◽  
pp. F416-F422 ◽  
Author(s):  
S. Omer ◽  
S. Mulay ◽  
P. Cernacek ◽  
D. R. Varma
Keyword(s):  
Atrial Natriuretic Factor ◽  
Collecting Duct ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Renal Effects ◽  
Natriuretic Factor ◽  
Sprague Dawley Rats ◽  
Collecting Duct Cells ◽  
Renal Responses ◽  
Atrial Natriuretic

The influence of pregnancy on renal responses to atrial natriuretic factor (ANF) was determined in urethane-anesthetized Sprague-Dawley rats. Infusions of ANF caused a significantly greater increase in urinary excretion of fluid, sodium, and potassium in virgin than in pregnant (13-15 days and 21 days) rats. Guanosine 3',5'-cyclic monophosphate (cGMP) excretion, mean arterial pressure, plasma immunoreactive ANF, and glomerular filtration rate (GFR) following ANF infusions were not different in virgin and gravid rats, although increments in GFR over basal were greater in virgin than in gravid animals. Renal responses to ANF normalized during postpartum and were attenuated by progesterone treatment of virgin rats. Natriuretic effects of infusions of ANF plus ANF-(4-23) (a ligand for clearance receptors) or of ANF plus thiorphan (an endopeptidase inhibitor) in virgin and pregnant rats did not differ; ANF-(4--23) and thiorphan alone caused greater natriuresis in pregnant than in virgin rats. Effects of ANF on cGMP production by collecting duct cells isolated from virgin and pregnant rats did not differ. We concluded that the attenuation in the renal effects of ANF during pregnancy might be mediated by progesterone by an increase in the intrarenal metabolism of ANF and might reflect physiological adjustment to facilitate fluid/electrolyte expansion.

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