Atrial Natriuretic Factor and Liver Disease

Abstract

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)

MELD score and clinical type predict prognosis in hepatorenal syndrome: Relevance to liver transplantation

“…(3) The plasma levels of atrial natriuretic peptide, a peptide released from the heart with potent vasodilator properties, are markedly higher in patients with type 1 compared with those in patients with type 2 HRS. The actual pathogenic significance of increased atrial natriuretic peptide levels in cirrhosis is unknown, but a role as mediator of splanchnic arterial vasodilation or antagonist of the effects of vasoconstrictor systems in the kidney has been proposed 48, 49. Taken together, these findings indicate that changes in the systemic arterial circulation of patients with type 1 and type 2 HRS are qualitatively similar but of different intensity.…”

Reversibly bound chloride in the atrial natriuretic peptide receptor hormone‐binding domain: Possible allosteric regulation and a conserved structural motif for the chloride‐binding site

“…For example, in transgenic animals overexpressing ANP, salt is retained despite the increased plasma ANP 7–10. In heart failure, plasma levels of ANP are markedly increased, yet sodium is retained 11–13. The mechanism underlying such apparent renal insensitivity to ANP is not understood.…”

Inhibition of cGMP-specific phosphodiesterase type 5 reduces sodium excretion and arterial blood pressure in patients with NaCl retention and ascites

“…kidney; sildenafil; viagra; ANP; renin A RELATIVE RESISTANCE TO THE natriuretic action of atrial natriuretic peptide (ANP) has been observed in sodium-retaining conditions such as nephrotic syndrome (40), congestive heart failure (35), and, in particular, cirrhosis of the liver. In liver cirrhosis the normal natriuretic effect of endogenous ANP or exogenously administered ANP 99 -126 is blunted (12,22,33,42). This phenomenon cannot be explained by the existence of a modified or less biologically active peptide in cirrhosis (17,38).…”

“…In liver cirrhosis the normal natriuretic effect of endogenous ANP or exogenously administered ANP 99 -126 is blunted (12,22,33,42). This phenomenon cannot be explained by the existence of a modified or less biologically active peptide in cirrhosis (17,38).…”