atrial-natriuretic-factor and Liver-Diseases

Patients with chronic liver disease (Läennec's cirrhosis) present sodium chloride retention, leading to fluid accumulation within the extracellular space (edema) and specially in the abdomen (ascites). This article reviews the pathogenesis of the hemodynamic abnormalities observed in these patients, particularly the hypothesis of "primary arterial vasodilation", with an increased nitric oxide production by endothelial cells playing a major role in the pathogenesis of vasodilation. Since excessive renal sodium reabsorption precedes ascites formation, two hypotheses are analyzed with respect to the handling of renal sodium in chronic liver disease: the underfilling and overflow theories. Furthermore, the role of natriuretic peptides is reviewed, the increment in atrial natriuretic peptide observed in well compensated cirrhotic patients being considered as a compensatory response to volume expansion, although with renal resistance to this peptide in early stages of the disease. This review ends with an integrated explanation of the circulatory disturbances, renal sodium retention and renal resistance to atrial natriuretic peptide resulting in the sodium and water abnormalities observed in chronic liver disease.

Topics: Animals; Ascites; Atrial Natriuretic Factor; Calcitonin Gene-Related Peptide; Chronic Disease; Humans; Kidney; Liver Cirrhosis; Liver Diseases; Natriuretic Agents; Nitric Oxide; Sodium; Vasodilation

The role of atrial natriuretic peptide (ANP) and potential defects of ANP in liver disease are reviewed. Patients with cirrhosis of the liver show no decrease of ANP plasma concentrations nor changes in the pattern of ANP immunoreactivity nor changes of splanchnic ANP clearance. The renal effects of exogenously administered as well as endogenously released ANP are blunted in cirrhosis, in particular in patients with ascites. This seems due to increased activity of sodium-retaining hormonal systems and changes of the renal ANP receptor status. Pharmacological inhibition of ANP-degradation or clearance may yield therapeutic potential.

Topics: Animals; Atrial Natriuretic Factor; Chronic Disease; Hemodynamics; Humans; Kidney; Liver Circulation; Liver Diseases

A working formulation for the role of ANF in the sodium retention of cirrhosis is summarized in Figure 4. Sodium retention is initiated early in cirrhosis, either as a result of hepatic venous outflow block or of primary vasodilation. The consequent intravascular volume expansion causes increases in ANF levels. At this stage of disease, the rise in ANF level is sufficient to counterbalance the antinatriuretic influences. However, this occurs at the expense of an expanded intravascular volume with the potential for overflow ascites. With progression of disease, disruption of intrasinusoidal Starling forces and loss of volume from the vascular compartment into the peritoneal compartment occur. This underfilling of the circulation may attenuate further increases in plasma ANF and promotes the activation of antinatriuretic factors. At this later stage of disease, elevated levels of ANF are insufficient to counterbalance antinatriuretic influences. Thus the role of ANF in cirrhosis is primarily beneficial in that it successfully attenuates the antinatriuretic forces in the compensated stage. Raised ANF levels have two potential deleterious effects. First, ANF may exacerbate arterial vasodilation, leading to further sodium retention. The primacy of vasodilatation has been proposed as an alternate formulation to the overflow and underfill hypotheses. Second, Epstein et al. found higher basal ANF levels in cirrhotic patients with edema than in those patients without edema. ANF is known to reduce plasma volume in anephric animals and to increase the ultrafiltration coefficients of isolated capillaries. Therefore it is conceivable that in the clinical setting in which antinatriuretic factors limit the renal responsiveness to ANF but in which ANF levels are elevated (i.e., cirrhosis, congestive heart failure, primary kidney disease), ANF itself may contribute to edema formation at the level of the peripheral microcirculation. In general, ANF likely has no primary role in the sodium retention in cirrhosis. In early compensated cirrhosis, ANF may maintain sodium homeostasis despite the presence of mild antinatriuretic factors. In late ascitic cirrhosis renal resistance to ANF develops, rendering it ineffective.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Animals; Arteries; Atrial Natriuretic Factor; Circadian Rhythm; Endopeptidases; Humans; Kidney; Liver Diseases; Natriuresis; Plasma Substitutes; Veins

The heart atrium, as well as under certain pathophysiological conditions the ventricle, synthesize and release ANP. Exerting natriuretic, diuretic and vasorelaxant effects, this peptide plays an important role in the body's blood volume and blood pressure homeostasis. Whereas the pharmacological actions of ANP have been quite convincingly demonstrated, its physiological and pathophysiological role is less well defined. ANP plasma levels tend to be increased in diseases with salt and water retention, such as essential hypertension, congestive heart failure, renal failure or liver cirrhosis. With regard to its hemodynamic effects, ANP seems to be beneficial in patients with hypertension. ANP appears to have little therapeutic potential as a diuretic in patients with congestive heart failure and liver cirrhosis, possibly due to the decreased renal responsiveness to ANP in these diseases. However, ANP might to be a valuable therapeutic agent in acute renal failure.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Heart Failure; Homeostasis; Humans; Hypertension; Kidney Diseases; Liver Diseases

Topics: Atrial Natriuretic Factor; Diuresis; Humans; Immersion; Liver Cirrhosis; Liver Diseases; Natriuresis; Peritoneovenous Shunt; Water-Electrolyte Balance

Topics: Atrial Natriuretic Factor; Cardiovascular Diseases; Humans; Kidney Diseases; Liver Diseases

The discovery of the first well-defined natriuretic hormone, the Atrial Natriuretic Factor (ANF), has prompted research on its impact on volume regulation in health and disease. The natriuretic, diuretic, and smooth muscle-relaxing properties suggest an important role of this novel hormone in pathophysiological states with sodium or volume retention, such as congestive heart failure or cirrhosis of the liver. Investigations on the implications of ANF in liver disease have been performed for little more than 1 year, and results are still controversial in many respects. At present, it seems very likely that there is no absolute deficiency of plasma ANF in patients with cirrhosis. Moreover, elevated plasma levels in cirrhotics with ascites have been reported by several groups. However, as yet, a molecular characterization of this increased immunoreactivity is still lacking. There is disagreement on the reduced release of and renal response to ANF in subgroups of cirrhotics; however, stimulus-response-coupling might be impaired. Further studies are needed to elucidate the pathophysiological implications and therapeutical potential of ANF in patients with chronic liver disease.

Topics: Atrial Natriuretic Factor; Blood Volume; Humans; Liver Cirrhosis; Liver Diseases; Water-Electrolyte Balance

The aim of this study was to evaluate hepatic dysfunction over 10 years following Fontan surgery. We assessed the clinical usefulness of diagnostic tools for the detection and follow-up of hepatic dysfunction in patients with Fontan circulation.A total of 26 post-Fontan patients (median age 13 years, range 10-35 years; median duration from Fontan procedure 10.5 years, range 4-17 years) were enrolled in this study. Hepatic assessment was performed by ultrasonography, computed tomography (CT), and transient elastography (TE) with biochemical tests, echocardiography, and cardiac catheterization. Related parameters were compared on the basis of different findings in liver sonography, CT, and TE.Liver CT and TE showed abnormal findings in all patients. Liver ultrasonography revealed abnormal results in 24 patients (92.3%). However, liver function test was normal and did not correlate with imaging studies. C-reactive protein was significantly correlated with severity of CT findings. White blood cell, platelet count, and N-terminal pro-brain natriuretic peptide were correlated with severity on TE. Post-Fontan high pulmonary vascular resistance (P = 0.046) and high mean pulmonary artery pressure (P = 0.046) correlated with hepatic changes on liver CT.Changes in the liver post-Fontan surgery are common and occur even after 10 years the procedure. Liver imaging is more sensitive, and CT seems to be more useful for differentiation of severe hepatic changes.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; C-Reactive Protein; Child; Child, Preschool; Early Diagnosis; Elasticity Imaging Techniques; Fontan Procedure; Humans; Liver; Liver Diseases; Liver Function Tests; Protein Precursors; Pulmonary Artery; Retrospective Studies; Severity of Illness Index; Tomography, X-Ray Computed; Ultrasonography; Vascular Resistance; Young Adult

Human atrial natriuretic peptide (ANP) is beneficial for the prophylaxis of acute renal failure (ARF) after liver transplantation (OLT). We evaluated renal function in OLT patients with or without ARF, describing cases unresponsive to loop diuretics successfully treated with continuous low-dose ANP infusion without hemodialysis. Twenty-seven consecutive adult-to-adult living donor liver transplantations (LDLTs) were performed in 26 patients. One case was excluded due to the need for continuous hemodialysis (HD) during the operation. Of the 26 cases, 6 (23%, group 2) developed ARF in the first 30 days after LDLT; the other 20 were ARF-free (group 1). The median follow-up was 24 months. No patient required either continuous or intermittent HD. Only one patient died due to multiple liver abscesses. Mean preoperative serum creatinine (sCr) value and intraoperative blood loss in group 2 were significantly higher than those in group 1. Three cases in group 2 failed to improve on high-dose loop diuretics with low-dose dopamine, exhibiting fluid overload. The remaining three cases in group 2 responded to conventional diuretic treatments. Continuous low-dose ANP was started 2, 4, or 5 days after LDLT, and urine output significantly increased after ANP administration. The serum creatinine values were 1.1, 1.2, and 1.1 at 1 month and 1.0, 0.9, and 0.6 mg/dL at 6 months after LDLT. Massive blood loss during the operation caused ARF, but did not affect renal function after LDLT. Continuous low-dose ANP improved renal function and diuresis for oliguric ARF patients, preventing the need for HD or continuous venovenous hemodialysis.

Topics: Adult; Atrial Natriuretic Factor; Blood Loss, Surgical; Diuresis; Female; Follow-Up Studies; Humans; Liver Diseases; Liver Transplantation; Living Donors; Male; Middle Aged; Oliguria; Postoperative Complications; Retrospective Studies

The generation of reactive oxygen species (ROS) by activated Kupffer cells contributes to liver injury following liver preservation, shock, or endotoxemia. Pharmacological interventions to protect liver cells against this inflammatory response of Kupffer cells have not yet been established. Atrial natriuretic peptide (ANP) protects the liver against ischemia-reperfusion injury, suggesting a possible modulation of Kupffer cell-mediated cytotoxicity. Therefore, we investigated the mechanism of cytoprotection by ANP during Kupffer cell activation in perfused rat livers of male Sprague-Dawley rats. Activation of Kupffer cells by zymosan (150 microgram/ml) resulted in considerable cell damage, as assessed by the sinusoidal release of lactate dehydrogenase and purine nucleoside phosphorylase. Cell damage was almost completely prevented by superoxide dismutase (50 U/ml) and catalase (150 U/ml), indicating ROS-related liver injury. ANP (200 nM) reduced Kupffer cell-induced injury via the guanylyl cyclase-coupled A receptor (GCA receptor) and cGMP: mRNA expression of the GCA receptor was found in hepatocytes, endothelial cells, and Kupffer cells, and the cGMP analog 8-bromo-cGMP (8-BrcGMP; 50 microM) was as potent as ANP in protecting from zymosan-induced cell damage. ANP and 8-BrcGMP significantly attenuated the prolonged increase of hepatic vascular resistance when Kupffer cell activation occurred. Furthermore, both compounds reduced oxidative cell damage following infusion of H2O2 (500 microM). In contrast, superoxide anion formation of isolated Kupffer cells was not affected by ANP and only moderately reduced by 8-BrcGMP. In conclusion, ANP protects the liver against Kupffer cell-related oxidant stress. This hormonal protection is mediated via the GCA receptor and cGMP, suggesting that the cGMP receptor plays a critical role in controlling oxidative cell damage. Thus ANP signaling should be considered as a new pharmacological target for protecting liver cells against the inflammatory response of activated Kupffer cells without eliminating the vital host defense function of these cells.

Topics: Animals; Atrial Natriuretic Factor; Catalase; Cyclic GMP; Endothelium, Vascular; Gene Expression; Guanylate Cyclase; Kupffer Cells; L-Lactate Dehydrogenase; Liver; Liver Diseases; Male; Oxidative Stress; Purine-Nucleoside Phosphorylase; Rats; Rats, Sprague-Dawley; Receptors, Atrial Natriuretic Factor; Reperfusion Injury; Superoxide Dismutase

Topics: Adult; Aged; Aldosterone; Anemia, Aplastic; Anemia, Iron-Deficiency; Atrial Natriuretic Factor; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Humans; Liver Diseases; Male; Medicine, Chinese Traditional; Middle Aged

Blunted volume expansion (VE) natriuresis and renal resistance to atrial natriuretic peptide (ANP) characterize states of pathological sodium retention. This study examined rats 1 to 3 wk after common bile-duct ligation (CBDL), at which time they had hyperbilirubinemia and hypoalbuminemia. Sham-operated normal rats (Sham) showed an increased sodium excretion rate (UNaV) from 1.0 +/- 0.1 to 16.3 +/- 3.9 muEq/min in response to acute VE (iv saline, 2 mL/100 g body wt over 5 min), whereas CBDL rats had a blunted response that was apparent after 1 wk and became maximal at 2 and 3 wk (0.3 +/- 0.1 to 3.2 +/- 0.4 muEq/min at 3 wk, P < 0.01 versus Sham response). The peak urinary cGMP excretion rate (UcGMPV) was also blunted (37.9 +/- 3.6 versus 87.5 +/- 8.3 pmol/min, P < 0.01) despite an even greater increase in plasma ANP concentration (Sham, 9.6 +/- 0.4 pg/mL in hydropenia to 22.8 +/- 2.6 pg/mL after VE; CBDL, 15.3 +/- 2.3 to 41.8 +/- 6.8 pg/mL). ANP-dependent cGMP accumulation by isolated inner medullary collecting duct (IMCD) cells from both Sham and CBDL rat kidneys was dose-dependent; however, at higher concentrations of ANP (> 10(-8) M), accumulation by cells from CBDL rats was significantly blunted, indicating resistance to ANP. Binding of 125I-ANP to IMCD cells was not different in CBDL rats compared with Sham control rats. Renal denervation improved but did not completely reverse the blunted natriuresis, and ANP resistance persisted in IMCD cells from denervated kidneys of CBDL rats. Incubation of IMCD cells with the phosphodiesterase inhibitors isomethylbutylxanthine or Zaprinast (each at 10(-3) M) restored ANP responsiveness in both innervated and denervated kidneys from CBDL rats, and intrarenal infusion of Zaprinast (10 micrograms/min) corrected the blunted increase in UNaV and UcGMPV after VE in rats with CBDL. These results suggest that ANP resistance in a model of abnormal sodium metabolism devoid of intrinsic renal disease may be related to increased activity of phosphodiesterase in renal target cells for ANP as well as to heightened renal nerve activity.

Topics: 1-Methyl-3-isobutylxanthine; Animals; Atrial Natriuretic Factor; Blood Volume; Common Bile Duct; Cyclic GMP; Drug Resistance; Kidney; Ligation; Liver Diseases; Male; Natriuresis; Nervous System; Phosphodiesterase Inhibitors; Purinones; Rats; Rats, Sprague-Dawley

Endothelin (ET) is a 21-amino-acid peptide of endothelial origin, is a potent systemic and renal vasoconstrictor associated with sodium retention and modulation of the renin-angiotensin-aldosterone system. The present study was designed to determine if plasma ET is elevated in humans with cirrhosis (n = 12), a state characterized by sodium retention and increased plasma renin activity (PRA) and plasma aldosterone (PA), and to determine the effect of orthotopic liver transplantation (OLT) upon plasma ET, PRA, and PA at 1, 3, and 7 days after transplantation. Plasma ET before OLT was 1.62 +/- 0.23 pg/ml, which was not different as compared with normal controls. Plasma ET significantly increased to 4.18 +/- 0.66, 3.87 +/- 0.58, and 4.07 +/- 0.61 pg/ml, respectively following OLT. PRA remained elevated throughout the postoperative course, in contrast to PA that decreased following OLT. Mean arterial pressure increased significantly from 82 +/- 4 pre-OLT to 98 +/- 4 and 103 +/- 2 mmHG on days 3 and 7 respectively.

Topics: Aldosterone; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Endothelins; Female; Humans; Hypertension; Liver Diseases; Liver Transplantation; Male; Middle Aged; Renin

The aim of this study was to assess the hormonal alterations that may mediate the systemic hypertension that develops in patients during the perioperative period of orthotopic liver transplantation. We studied nine pediatric patients without previous hypertension or renal disease during six time points, starting before transplantation and ending at 48 hours after surgery. Hypertension developed in all patients in association with central venous pressures less than 10 mm Hg. Free water clearance was negative in all nine patients. Vasopressin levels increased intraoperatively but fell as hypertension developed. Atrial natriuretic factor levels increased as systemic blood pressure rose. A high level of plasma renin activity was observed in four patients with renal insufficiency. In six patients, postoperative 24-hour urinary norepinephrine excretion was within the normal age-adjusted range. These findings suggest that the combination of cyclosporine, corticosteroids, and, in some patients, an elevated plasma renin activity prevents the kidney from responding to the acute volume and salt overload with an appropriate diuresis and natriuresis, thus leading to systemic hypertension. The treatment of hypertension after liver transplantation may include salt restriction, diuretics, and, in those patients with a low creatinine excretion index, angiotensin coverting enzyme inhibitors.

Topics: Adolescent; Arginine Vasopressin; Atrial Natriuretic Factor; Child; Child, Preschool; Creatinine; Cyclosporins; Humans; Hypertension; Intraoperative Period; Liver Diseases; Liver Transplantation; Norepinephrine; Renin; Sodium

The plasma levels of atrial natriuretic peptide were determined by radioimmunoassay in 24 patients with chronic liver disease, including three patients with alcoholic liver disease, four with chronic active hepatitis, 13 with liver cirrhosis, and four with hepatocellular carcinoma. When compared with normal subjects (180 +/- 12 pg/ml), the plasma levels of atrial natriuretic peptide in cirrhotic patients (349 +/- 64 pg/ml) were significantly elevated (p less than 0.001) but not in other disease groups. In patients with chronic liver disease the plasma levels of atrial natriuretic peptide were correlated significantly with plasma renin activity but not with plasma aldosterone, and furthermore showed a negative correlation with indocyanine green disappearance rate. These results suggest that the increased plasma levels of atrial natriuretic peptide, which appear to be associated with an increase in plasma renin activity and with hepatic dysfunction, may participate in maintaining homeostasis of sodium and fluid volume in patients with chronic liver disease.

Topics: Aldosterone; Atrial Natriuretic Factor; Carcinoma, Hepatocellular; Chronic Disease; Female; Hepatitis, Chronic; Humans; Liver Cirrhosis; Liver Diseases; Liver Diseases, Alcoholic; Liver Function Tests; Liver Neoplasms; Male; Middle Aged; Radioimmunoassay

Using a radioimmunoassay for atrial natriuretic peptide (ANP) we studied plasma concentrations of immunoreactive ANP in order to investigate the pathophysiological role of ANP in patients with various diseases. Plasma ANP levels were elevated in patients with congestive heart failure (394 +/- 260 pg/ml, n = 8) and chronic renal failure (219 +/- 86 pg/ml, n = 11). In patients undergoing hemodialysis plasma ANP levels were markedly high and decreased after hemodialysis from 433 +/- 166 pg/ml to 204 +/- 92 pg/ml (n = 11). ANP was removed from blood to dialysate (21 +/- 13 pg/ml of dialysate, n = 6, dialysate flow: 500 ml/min). Plasma ANP level was conversely correlated with creatinine clearance (r = -0.812, p less than 0.001) in patients with renal diseases (n = 29). In patients with atrial fibrillation, pace maker implantation, lung disease, chronic glomerulonephritis, nephrotic syndrome, essential hypertension, liver disease and cerebrovascular disease, plasma ANP levels were not significantly different from those in normal subjects (70 +/- 32 pg/ml, n = 28). These results suggest that ANP may be a circulating hormone playing pathophysiological roles in congestive heart failure and chronic renal failure.

Topics: Adult; Atrial Natriuretic Factor; Cardiovascular Diseases; Cerebrovascular Disorders; Chronic Disease; Female; Humans; Kidney Diseases; Liver Diseases; Lung Diseases, Obstructive; Male; Middle Aged; Radioimmunoassay; Renal Dialysis