Biochemical mechanisms of atrial natriuretic factor action

1989 ◽  
Vol 67 (9) ◽  
pp. 1124-1129 ◽  
Author(s):  
Johanne Tremblay ◽  
Pavel Hamet
Keyword(s):  
Heart Failure ◽  
Guanylate Cyclase ◽  
Atrial Natriuretic Factor ◽  
Soluble Guanylate Cyclase ◽  
Membrane Glycoprotein ◽  
Natriuretic Factor ◽  
Biochemical Mechanisms ◽  
Stimulation Of ◽  
Atrial Natriuretic

Since atrial natriuretic factor (ANF) is a natriuretic and vasodilatory hormone, its mechanisms of action expectedly involve so-called negative pathways of cell stimulation, notably cyclic nucleotides. Indeed, the guanylate cyclase–cyclic GMP (cGMP) system appears to be the principal mediator of ANF's action. Specifically, particulate guanylate cyclase, a membrane glycoprotein, transmits ANF's effects, as opposed to the activation of soluble guanylate cyclase by such agents as sodium nitroprusside. The stimulation of particulate guanylate cyclase by ANF manifests several characteristics. One of them is the functional irreversibility of stimulation with its apparent physiological consequences: the extended impact of ANF on diuresis and vasodilation in vivo lasts beyond the duration of increased plasma ANF levels and is accompanied by a prolonged elevation of cGMP. Another characteristic is the parallelism between guanylate cyclase stimulation and increases of cGMP in extracellular fluids. cGMP egression appears to be an active process, yet its physiological implications remain to be uncovered. In heart failure, cGMP continues to reflect augmented ANF levels, suggesting that in this disease, the lack of an ANF effect on sodium excretion is due to a defect distal to cGMP generation. In hypertension, where ANF levels are either normal or slightly elevated, probably secondary to high blood pressure, the ANF responsiveness of the particulate guanylate cyclase–cGMP system, the hypotensive effects, diuresis and natriuresis are exaggerated. The implications of this exaggerated responsiveness of the ANF–cGMP system in the pathophysiology of hypertension and its potential therapeutic connotations remain to be evaluated.Key words: ANF, cGMP, guanylate cyclase, hypertension, heart failure.

scholarly journals Stimulation of guanylate cyclase by atrial natriuretic factor in isolated human glomeruli

FEBS Letters ◽  
1985 ◽  
Vol 189 (1) ◽  
pp. 8-12 ◽  
Author(s):  
Nicole Ardaillou ◽  
Marie-Paule Nivez ◽  
Raymond Ardaillou
Keyword(s):  
Guanylate Cyclase ◽  
Atrial Natriuretic Factor ◽  
Natriuretic Factor ◽  
Stimulation Of ◽  
Atrial Natriuretic

scholarly journals Atrial natriuretic factor and sodium nitroprusside increase cyclic GMP in cultured rat lung fibroblasts by activating different forms of guanylate cyclase

1987 ◽  
Vol 244 (1) ◽  
pp. 69-74 ◽  
Author(s):  
D C Leitman ◽  
V L Agnost ◽  
J J Tuan ◽  
J W Andresen ◽  
F Murad
Keyword(s):  
Sodium Nitroprusside ◽  
Guanylate Cyclase ◽  
Cyclic Gmp ◽  
Atrial Natriuretic Factor ◽  
Soluble Guanylate Cyclase ◽  
Fold Increase ◽  
Lung Fibroblasts ◽  
Rat Lung ◽  
Natriuretic Factor ◽  
Stimulation Of

We used cultured rat lung fibroblasts to evaluate the role of particulate and soluble guanylate cyclase in the atrial natriuretic factor (ANF)-induced stimulation of cyclic GMP. ANF receptors were identified by binding of 125I-ANF to confluent cells at 37 degrees C. Specific ANF binding was rapid and saturable with increasing concentrations of ANF. The equilibrium dissociation constant (KD) was 0.66 +/- 0.077 nM and the Bmax. was 216 +/- 33 fmol bound/10(6) cells, which corresponds to 130,000 +/- 20,000 sites/cell. The molecular characteristics of ANF binding sites were examined by affinity cross-linking of 125I-ANF to intact cells with disuccinimidyl suberate. ANF specifically labelled two sites with molecular sizes of 66 and 130 kDa, which we have identified in other cultured cells. ANF and sodium nitroprusside produced a time- and concentration-dependent increase in intracellular cyclic GMP. An increase in cyclic GMP by ANF was detected at 1 nM, and at 100 nM an approx. 100-fold increase in cyclic GMP was observed. Nitroprusside stimulated cyclic GMP at 10 nM and at 1 mM a 500-600-fold increase in cyclic GMP occurred. The simultaneous addition of 100 nM-ANF and 10 microM-nitroprusside to cells resulted in cyclic GMP levels that were additive. ANF increased the activity of particulate guanylate cyclase by about 10-fold, but had no effect on soluble guanylate cyclase. In contrast, nitroprusside did not alter the activity of particulate guanylate cyclase, but increased the activity of soluble guanylate cyclase by 17-fold. These results demonstrate that rat lung fibroblasts contain ANF receptors and suggest that the ANF-induced stimulation of cyclic GMP is mediated entirely by particulate guanylate cyclase.

Leukotriene D4 inhibits atrial natriuretic factor-dependent cGMP production in rat glomerulus

1989 ◽  
Vol 256 (1) ◽  
pp. F95-F99
Author(s):  
Y. Terada ◽  
K. Tomita ◽  
N. Yoshiyama ◽  
T. Shiigai ◽  
F. Marumo
Keyword(s):  
Sodium Nitroprusside ◽  
Guanylate Cyclase ◽  
Atrial Natriuretic Factor ◽  
Soluble Guanylate Cyclase ◽  
Leukotriene D4 ◽  
Isolated Glomeruli ◽  
Cgmp Production ◽  
Natriuretic Factor ◽  
Isolated Rat ◽  
Atrial Natriuretic

The effects of leukotriene D4 (LTD4) on guanosine 3',5'-cyclic monophosphate (cGMP) production induced by atrial natriuretic factor (ANF) or sodium nitroprusside (SNP) were investigated in isolated rat glomeruli. First, the isolated glomeruli were preincubated in Krebs-Ringer buffer containing 3-isobutyl-1-methylxanthine for 10 min, then incubated with varying concentrations of ANF, SNP, and LTD4 for 3 min. cGMP content was determined by radioimmunoassay. cGMP production (fmol.glomerulus-1.3 min-1) was not increased by LTD4. cGMP accumulation was increased by ANF (1 microM) and SNP (100 microM) remarkably from 0.19 +/- 0.09 to 3.24 +/- 0.21 (n = 7, mean +/- SE), and from 0.19 +/- 0.09 to 3.67 +/- 0.47 (n = 4), respectively. The increase in cGMP production by ANF was significantly and dose-dependently inhibited by LTD4 (P less than 0.05). Maximum suppression was observed at the concentration of 100 nM (from 3.06 +/- 0.33 to 1.43 +/- 0.09; P less than 0.05). However, LTD4 caused no significant change in the level of cGMP production induced by SNP. Second, particulate or soluble guanylate cyclase from glomeruli were similarly investigated. ANF selectively activated particulate guanylate cyclase and the response was selectively inhibited by LTD4 from 9.07 +/- 1.79 fmol.micrograms-1.3 min-1 (n = 6) to 4.70 +/- 0.70 (n = 6, P less than 0.05). These results suggest the site where LTD4 has effect on cGMP production induced by ANF was the particulate guanylate cyclase system, but not the soluble guanylate cyclase system.

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.

Neural influences on renal responses to acute volume expansion in rats with heart failure

1996 ◽  
Vol 271 (4) ◽  
pp. H1441-H1448 ◽  
Author(s):  
K. P. Patel ◽  
P. L. Zhang ◽  
P. K. Carmines
Keyword(s):  
Heart Failure ◽  
Atrial Natriuretic Factor ◽  
Volume Expansion ◽  
Renal Nerve ◽  
Natriuretic Factor ◽  
Renal Nerve Activity ◽  
Neural Influences ◽  
Renal Responses ◽  
Renal Sympathetic ◽  
Atrial Natriuretic

Experiments were performed to test the postulate that neural influences underlie the suppressed excretory response to acute volume expansion (VE) typically observed 3-4 wk after myocardial infarction to induce chronic heart failure (CHF). Responses to VE were assessed in innervated (intact) and denervated (DNX) kidneys of anesthetized CHF rats and sham-operated controls. CHF rats exhibited blunted natriuretic responses to VE in both intact kidneys (35% of sham response) and DNX kidneys (55% of sham DNX response). CHF rats also displayed suppressed excretory responses to atrial natriuretic factor (0.25 microgram.kg-1.min-1 iv) in both intact kidneys (74% of sham response) and DNX kidneys (63% of sham DNX response). Additional experiments confirmed that the compliance of the venoatrial junction did not differ between sham rats (52 +/- 2 mmHg/microliter) and CHF rats (54-2 mmHg/microliter). The observations support the contention that both tonic renal sympathetic renal nerve activity and suppressed renal atrial natriuretic factor responsiveness likely contribute to the blunted excretory response to VE during CHF.

Effects of clonidine and dihydralazine on atrial natriuretic factor and cGMP in humans

1989 ◽  
Vol 67 (3) ◽  
pp. 938-944 ◽  
Author(s):  
M. Wehling ◽  
T. Muller ◽  
J. M. Heim ◽  
R. Lorenz ◽  
H. Witzgall ◽  
...  
Keyword(s):  
Atrial Natriuretic Factor ◽  
Soluble Guanylate Cyclase ◽  
Normal Subjects ◽  
Treated Group ◽  
Base Line ◽  
Hemodynamic Effects ◽  
Volume Loading ◽  
Natriuretic Factor ◽  
Basal Plasma ◽  
Atrial Natriuretic

The effects of a 1-wk treatment with clonidine (75 micrograms/day twice a day) and dihydralazine (25 mg/day twice a day) on base-line levels of plasma atrial natriuretic factor (ANF) and plasma and urinary guanosine 3′,5′-cyclic monophosphate (cGMP) and their changes by acute saline infusion (2 liters) in eight normal subjects were evaluated. Basal ANF was decreased to 65% in the clonidine group compared with both the control and dihydralazine groups. Volume loading increased plasma ANF levels by 30–40% of base-line values in the control and the dihydralazine groups and by 15% in the clonidine group. Basal plasma and urinary cGMP levels were raised by 30 and 90% in the dihydralazine group compared with both other groups. Volume loading increased plasma cGMP levels by 40% in the control and clonidine-treated groups and by 25% in the dihydralazine-treated group. It is concluded that ANF may contribute to hemodynamic effects of clonidine but not to those of dihydralazine. Dihydralazine increases plasma and urinary cGMP, supposedly by direct activation of the soluble guanylate cyclase.

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