scholarly journals Contribution of blood and systemic circulation to the processing of pro-(atrial natriuretic factor)

1988 ◽  
Vol 250 (3) ◽  
pp. 665-670 ◽  
Author(s):  
K K Murthy ◽  
G Thibault ◽  
M Cantin
Keyword(s):  
Atrial Natriuretic Factor ◽  
Secretory Granules ◽  
Systemic Circulation ◽  
Initial Distribution ◽  
Metabolic Clearance ◽  
Time Intervals ◽  
Natriuretic Factor ◽  
Atrial Cardiocytes ◽  
Hydrolysis Of ◽  
Atrial Natriuretic

Atrial natriuretic factor-(Asn1-Tyr126)-peptide, the 13.6 kDa propeptide of atrial natriuretic factor (ANF), is stored in the secretory granules of atrial cardiocytes. ANF-(Ser99-Tyr126)-peptide, the 28-amino-acid species, is the circulating form of this hormone in the rat. As the site of maturation of the prohormone is still unknown, the present study was undertaken to understand the contribution of the circulation to the maturation process of pro-ANF. 125I-ANF-(Asn1-Tyr126)-peptide was incubated with whole rat blood, plasma or serum for different time intervals, and the products were analysed. There was minimal activation of the propeptide in either whole blood or plasma. Incubation with serum, however, resulted in the formation of an 11 kDa and a 3 kDa peptide which corresponded respectively to the N-terminal and C-terminal parts of the propeptide. These results suggest that hydrolysis of the propeptide in serum is brought about by enzymes that may be stimulated during coagulation but which may not play a major role in the activation of pro-ANF in the circulation. Plasma analysis at different time intervals after prohormone injection indicated a non-specific hydrolysis of the pro-ANF molecule. The disappearance rate curves, obtained with radiolabelled pro-ANF, suggested the presence of two components with half-lives of 2.1 +/- 0.4 min and 52.5 +/- 8.4 min respectively. A metabolic clearance rate of 1.49 +/- 0.22 ml/min and an initial distribution volume of 47.4 +/- 8 ml were calculated. These results indicate that the maturation of pro-ANF to its active circulating form takes place before it is released into the circulation.

Clearance function of type C receptors of atrial natriuretic factor in rats

1989 ◽  
Vol 256 (2) ◽  
pp. R469-R475 ◽  
Author(s):  
F. A. Almeida ◽  
M. Suzuki ◽  
R. M. Scarborough ◽  
J. A. Lewicki ◽  
T. Maack
Keyword(s):  
Atrial Natriuretic Factor ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Natriuretic Factor ◽  
Initial Plasma ◽  
Acid Solubility ◽  
Type C ◽  
Dose Dependent ◽  
Hydrolysis Of ◽  
Atrial Natriuretic

The overwhelming majority of atrial natriuretic factor (ANF) receptors in kidney and vascular tissues do not mediate any of the known functional effects of the hormone. To test whether these receptors (C-ANF receptors) function as clearance receptors for circulating ANF-(1-28), we determined the effects of C-ANF-(4-23) [des[Gln18Ser19Gly20Leu21Gly22]rANF-(3-23)-NH2], a specific ligand of C-ANF receptors, on the pharmacokinetics and hydrolysis of 125I-labeled ANF-(1-28) in anesthetized rats. Radioactivity in plasma was characterized by trichloroacetic acid solubility and high-pressure liquid chromatography. C-ANF-(4-23) (1 and 10 micrograms.min-1.kg body wt-1) led to marked dose-dependent increases in initial plasma concentration of administered 125I-ANF-(1-28) and decreases in its volume of distribution at steady state (Vss), metabolic clearance rate (MCR), and appearance of hydrolytic products ([125I]monoiodotyrosine and free 125I) in plasma (Pm). At the highest dose, C-ANF-(4-23) decreased Vss from 97 +/- 12 to 36 +/- 2 ml/100 g body wt, MCR from 50 +/- 4 to 12 +/- 1 ml.min-1.100 g body wt-1, and Pm from 54 +/- 8 to 11 +/- 2% of initial plasma 125I-ANF-(1-28). The data demonstrate that C-ANF receptors are mainly responsible for the very large volume of distribution and fast MCR of ANF in the rat. In this manner, C-ANF receptors are likely to play an important role in the homeostasis of circulating ANF.

scholarly journals Atrial natriuretic factor in the vena cava and sinus node.

1990 ◽  
Vol 38 (8) ◽  
pp. 1123-1135 ◽  
Author(s):  
C Sola ◽  
G Thibault ◽  
H Haile-Meskel ◽  
M B Anand-Srivastava ◽  
R Garcia ◽  
...  
Keyword(s):  
Superior Vena Cava ◽  
Atrial Natriuretic Factor ◽  
Secretory Granules ◽  
Superior Vena ◽  
Sinus Node ◽  
Vena Cava ◽  
Natriuretic Factor ◽  
Atrial Cardiocytes ◽  
Transitional Cells ◽  
Atrial Natriuretic

We investigated the localization of atrial natriuretic factor (ANF) mRNA and of immunoreactive ANF in the vena cava and sinus node of rat and, for comparative purposes, in atria and ventricles. In situ hybridization with an ANF cRNA probe revealed that the supradiaphragmatic portion of the inferior vena cava contains almost as much mRNA as the atria, whereas the levels were less in the superior vena cava and higher than in ventricles in the sinus node. Immunoreactive ANF (high Mr form) was found to be 22 times less abundant in the supradiaphragmatic vena cava and 148 times less abundant in the superior vena cava than in atrial cardiocytes. The wall of the supradiaphragmatic portion of the vena cava and the valve (eustachian valve) that separates the atrial cavity from that of the vein are made up of atrial-like cardiocytes containing secretory granules. The subendothelial area of the superior vena cava also contains atrial-like cardiocytes with secretory granules, whereas the outer portion of the vein is made up of "transitional cells" without or with only a few secretory granules. Secretory granules in the vena cava and nodal cells, as well as transitional cells, contain immunoreactive ANF. With immunocryoultramicrotomy, virtually all cells, whether atrial-like, transitional, or nodal, and even those without secretory granules, were found to contain immunoreactive ANF in their Golgi complex and in secretory vesicles in the vena cava and in the sinus node.

Metabolic clearance of atrial natriuretic factor in ovine pregnancy

1994 ◽  
Vol 267 (5) ◽  
pp. R1413-R1420
Author(s):  
S. Mukaddam-Daher ◽  
J. Gutkowska ◽  
B. S. Nuwayhid ◽  
E. W. Quillen
Keyword(s):  
Atrial Natriuretic Factor ◽  
Volume Expansion ◽  
High Performance ◽  
Degradation Products ◽  
Initial Distribution ◽  
Metabolic Clearance ◽  
Plasma Decay ◽  
Natriuretic Factor ◽  
Pregnant Sheep ◽  
Atrial Natriuretic

Plasma atrial natriuretic factor (ANF) is normally released into the circulation primarily by volume expansion and atrial distension, but we have shown that plasma ANF is elevated in pregnant sheep before volume expansion. Because alterations in the metabolic clearance of ANF could lead to elevated plasma ANF levels, the present study was designed to determine the pharmacokinetics of plasma ANF in pregnant sheep. Chronically instrumented nonpregnant and pregnant sheep received intravenous injections of monoiodinated human ANF (125I-hANF). Plasma decay curves of 125I-hANF followed a biexponential function in both groups. High-performance liquid chromatography (HPLC) revealed the accumulation of smaller degradation products by 2 min postinjection, and by 30 min no intact ANF was present. Because HPLC identification of ANF and its metabolites was shown to be more efficient than precipitation with 10% trichloroacetic acid (TCA) or extraction by Sep-Pak cartridges, ANF kinetic parameters were calculated from HPLC-corrected plasma decay curves. Injected ANF was rapidly distributed in an initial distribution volume (IDV) that was expanded in pregnant sheep. Metabolic clearance rate (MCR) was greater in pregnant sheep (2.8 +/- 0.3 vs. 6.8 +/- 1.2 l/min, P = 0.002), while plasma half-life (t1/2) was not altered (2.2 +/- 0.5 vs. 2.4 +/- 0.4 min). The data demonstrate that during pregnancy, the t1/2 of ANF is not altered but the MCR of ANF is enhanced. These findings imply that plasma ANF is increased by mechanisms other than reduced clearance in pregnant sheep.

Regulated secretion of atrial natriuretic factor from cultured ventricular myocytes

1993 ◽  
Vol 264 (1) ◽  
pp. H282-H285 ◽  
Author(s):  
C. E. Irons ◽  
C. A. Sei ◽  
C. C. Glembotski
Keyword(s):  
Transit Time ◽  
Atrial Natriuretic Factor ◽  
Ventricular Myocytes ◽  
Secretory Granules ◽  
Subcellular Fractionation ◽  
Neonatal Rat ◽  
Cell Type ◽  
Regulated Secretion ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

We have investigated endothelin (ET)-regulated secretion of atrial natriuretic factor (ANF) from primary neonatal rat ventricular myocytes, where hormone release is thought to be constitutive. In a dose-dependent, nifedipine-sensitive manner, ET acutely enhanced ANF release by two- to fivefold over control cultures within 15 min of agonist exposure, demonstrating that ventricular myocytes display a primary characteristic of a regulated secretory cell type. Unlike atrial cultures, ET enhanced ANF release during the first 30 min of exposure; thereafter, secretion rates returned to control levels. KCl, however, effectively enhanced ANF release only during the first 15 min of exposure. Subcellular fractionation of ventricular culture homogenates did not reveal atrial-type dense secretory granules, and pulse-chase labeling experiments showed that the transit time of newly synthesized ANF was short in ventricular myocytes [time required for half of labeled ANF to be released from cells (t1/2) = 0.5-1.5 h) compared with atrial myocytes (t1/2 = 4 h). These results suggest that, whereas ventricular myocytes possess some of the characteristics of a constitutively secreting cell type (e.g., few, if any, dense secretory granules and rapid transit time for newly synthesized hormone); however, they also display the capacity for regulated secretion of ANF in response to the physiological agonist ET.

scholarly journals The propeptide Asn1–Tyr126 is the storage form of rat atrial natriuretic factor

1987 ◽  
Vol 241 (1) ◽  
pp. 265-272 ◽  
Author(s):  
G Thibault ◽  
R Garcia ◽  
J Gutkowska ◽  
J Bilodeau ◽  
C Lazure ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Atrial Natriuretic Factor ◽  
Secretory Granules ◽  
Activity Analysis ◽  
Differential Centrifugation ◽  
Percoll Gradient ◽  
Cell Debris ◽  
Glucuronidase Activity ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

Granules from rat atria were isolated by differential centrifugation and by a 53% (v/v) Percoll gradient after tissue homogenization in 0.25 M-sucrose/50 mM-Na2EDTA. About 40% of the immunoreactive ANF (atrial natriuretic factor) sedimented with the atrial granules during differential centrifugations. On the Percoll gradient, two distinct bands were observed. Cell debris, mitochondria, lysosomes, myofilaments and microsomes were mostly contained in the lightest-density (rho) (1.03-1.07 g/ml) fraction, as demonstrated by electron microscopy and by enzymic markers such as lactate dehydrogenase, monoamine oxidase, cytochrome c reductase, beta-glucuronidase and acid phosphatase. Atrial granules were mostly contained in the denser (rho 1.11-1.15 g/ml) band and were only slightly contaminated by lysosomes, as shown by beta-glucuronidase activity. Analysis of the ANF content in these isolated granules by h.p.l.c., amino acid composition and sequencing demonstrated that it was only the pro-ANF [ANF-(Asn1-Tyr126)-peptide]. The precursor was present in all granules, as demonstrated by immunocytochemistry. Since hormonal propeptides usually undergo intracellular processing, and the matured peptides are subsequently stored in the secretory granules, these results indicate that the processing pathway of ANF may be different from that of other hormonal peptides.

Phosphorylation State of pro-Atrial Natriuretic Factor in Rat Atrial Secretory Granules*

Endocrinology ◽  
1990 ◽  
Vol 127 (6) ◽  
pp. 2839-2848 ◽  
Author(s):  
G. M. WILDEY ◽  
A. J. FISCHMAN ◽  
M. N. MARGOLIES ◽  
R. M. GRAHAM ◽  
C. J. HOMCY
Keyword(s):  
Atrial Natriuretic Factor ◽  
Secretory Granules ◽  
Phosphorylation State ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

Renal dose response and pharmacokinetics of atrial natriuretic factor in dogs

1988 ◽  
Vol 255 (6) ◽  
pp. R929-R935
Author(s):  
P. Cernacek ◽  
E. Maher ◽  
J. C. Crawhall ◽  
M. Levy
Keyword(s):  
Atrial Natriuretic Factor ◽  
Renal Plasma Flow ◽  
Constant Infusion ◽  
Slow Phase ◽  
Pharmacokinetic Parameters ◽  
Metabolic Clearance ◽  
Rapid Phase ◽  
Natriuretic Factor ◽  
Dose Dependent ◽  
Atrial Natriuretic

The present studies investigated the dose-plasma level-response relationships with the use of increasing doses of atrial natriuretic factor [ANF-(99-126)] administered by constant infusion in conscious dogs. The preinfusion plasma immunoreactive ANF increased 12, 19, 23, and 35 times during 45-min consecutive infusions of 50, 75, 125, and 175 ng.kg-1.min-1, respectively. Over this pharmacological range, natriuresis increased linearly with the infused dose (r = 0.99, n = 5) to a maximum response of +1,550%, despite the significant gradual fall of blood pressure, which attained a minimum of 83 mmHg (-26%) at 125 ng.kg-1.min-1. There was no change of glomerular filtration rate (GFR) or renal plasma flow at any dose. A very similar renal response was found in 13 other dogs infused with the highest dose only in which the pharmacokinetic parameters of ANF-(99-126) were estimated. Metabolic clearance rate during the infusion was 1.09 +/- 0.19 l/min. The postinfusion decay curve of plasma immunoreactive ANF was best described by a biexponential function. Plasma disappearance half time was 1.44 min during the rapid phase and 10.3 min during the slow phase of elimination. The results show that 1) natriuretic response to ANF in the pharmacological range is dose dependent and occurs despite a pronounced hypotension, 2) increase in GFR is not a prerequisite of ANF-induced natriuresis, and 3) ANF is rapidly eliminated from the circulation, suggesting an intensive uptake and/or degradation in the target tissues.

Analysis of atrial natriuretic factor biosynthesis and secretion in adult and neonatal rat atrial cardiocytes

Life Sciences ◽  
1987 ◽  
Vol 41 (16) ◽  
pp. 1953-1959 ◽  
Author(s):  
Jerome B. Zisfein ◽  
Diana Sylvestre ◽  
Charles J. Homcy ◽  
Robert M. Graham
Keyword(s):  
Atrial Natriuretic Factor ◽  
Neonatal Rat ◽  
Natriuretic Factor ◽  
Atrial Cardiocytes ◽  
Atrial Natriuretic
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