CIRRHOSIS WITH ASCITES - INCREASED ATRIAL-NATRIURETIC-PEPTIDE MESSENGER-RNA EXPRESSION IN RAT VENTRICLE

Background/Aims: Atrial natriuretic peptides (ANPs) are increased in the circulation of cirrhotics with ascites; however, it is unknown whether this increase is caused by increased synthesis or a decrease in the metabolic processing of these peptides. ANP gene expression in the liver, atria, ventricles, and gastrointestinal tract of cirrhotic vs. control rats was studied as was their metabolism. Methods: Sprague-Dawley rats developed cirrhosis with ascites approximately 20 weeks after weekly intragastric instillation of carbon tetrachloride. Their circulating, ascitic, and urinary levels of ANPs were measured by radioimmunoassays. ANP gene expression was measured by a ribonuclease protection assay. Results: ANP gene expression was increased 2.8- to 4.1-fold in the ventricles of cirrhotic rats compared with age-matched healthy rats. ANP gene expression was present but not increased in the liver, atria, and gastrointestinal tract of cirrhotic rats. No increase of metabolic processing of these peptides was found in the circulation. Cardiac ultrasonography and catheterization revealed no ventricular dilation or increased ventricular pressure. Conclusions: Elevation of circulating ANPs with cirrhosis was associated with increased ventricular steady-state ANP messenger RNA concentrations. The increased ANP gene expression in cirrhosis seems to involve a novel mechanism not related to stretch because neither increased ventricular pressure nor dilation was present.