Uncoupling of atrial natriuretic peptide and cyclic guanosine 3',5'-monophosphate production in patients with liver cirrhosis.

Abstract

Atrial natriuretic peptide (ANP) concentrations within the reference interval have been reported in patients with alcoholic liver disease, chronic active hepatitis, and hepatocellular carcinoma. Markedly increased ANP concentrations, by contrast, have been found in patients with liver cirrhosis [3]. Exogenously administered ANP has been found to elevate the plasma concentration of its second messenger cyclic guanosine monophosphate (cGMP) in accordance with its physiological effects [4]. Therefore, cGMP increase in plasma can be regarded as a marker for the biological activities of ANP. Because of contradictory reports [2, 3, 5] on ANP in liver cirrhosis we investigated plasma ANP and cGMP concentrations to assess the biological activity of ANP in liver cirrhosis. Plasma ANP concentrations were determined in 124 healthy volunteers (72 males, 52 females) aged 20 64 years (40 _+ 12 years) and plasma cGMP concentrations in 147 healthy blood donors (92 males, 55 females) aged 15-62 years (34+_ 13 years). Plasma ANP and cGMP concentrations were determined in 15 patients with liver cirrhosis (7 males, 8 females) aged 31-69 years (54_+ 14 years). Five patients had ascites. The underlying cause of cirrhosis was cq-antitrypsin deficiency in 4 patients, alcohol abuse in 7, chronic hepatitis in 2, and unknown in 2. Creatinine concentrations in plasma were within the normal range (79.56 -+ 9.547 p.mol/1, range: 66.3-101.66 pmol/1) in all patients. Plasma cGMP concentrations were determined by radioimmunoassay (Amersham International, Amersham, Buckinghamshire, UK), and ANP concentrations in plasma were measured by means of a commercially available radioimmunoassay (Eiken, Tokyo, Japan) without extraction [1]. Results are expressed as mean _+ SD. Groups were compared statistically using Mann-Whitney U test; significance was defined as P<0.05. Plasma cGMP concentrations in patients with liver cirrhosis (4.448_+2.022 nmol/1, range 0.5-8.28 nmot/1, n = 15) did not differ significantly from those in healthy controls (4.637_+ 1.533nmol/1, range, 1.88~.04nmol/1, n=147, P=0.9426; Fig. 1). By contrast, plasma ANP concentrations were significantly higher in patients with cirrhosis (213.867_+83.032 ng/1, range 107-389ng/1, n=15) than in healthy controls (69.5_+ 26.05 ng/1, range 18-151 ng/1, n = 124, P=0.0001; Fig. 1). In the group of patients with liver cirrhosis no significant difference in plasma ANP (206.2_+59.437 versus 217.7-+95.422, P = I ) or plasma cGMP (5.656-+1.804 versus 3.777_+1.897, P=0.142) concentrations were detectable between patients with and patients without ascites. We found increased immunoreactive ANP concentrations without a concomitant increase in plasma cGMP in our patients with liver cirrhosis. In accordance with earlier reports we found no significant difference in plasma concentrations of ANP [3]