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 ◽  
...  

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.

1989 ◽  
Vol 256 (2) ◽  
pp. G436-G441 ◽  
Author(s):  
C. Bianchi ◽  
G. Thibault ◽  
A. De Lean ◽  
J. Genest ◽  
M. Cantin

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.


1988 ◽  
Vol 254 (5) ◽  
pp. R809-R814 ◽  
Author(s):  
A. T. Veress ◽  
S. Milojevic ◽  
C. Yip ◽  
T. G. Flynn ◽  
H. Sonnenberg

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.


Endocrinology ◽  
1987 ◽  
Vol 121 (1) ◽  
pp. 248-257 ◽  
Author(s):  
JINFENG DING ◽  
GAÉTAN THIBAULT ◽  
JOLANTA GUTKOWSKA ◽  
RAUL GARCIA ◽  
THEODORE KARABATSOS ◽  
...  

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