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

Background/Aims: Atrial natriuretic peptides (ANPs) are increased in t he circulation of cirrhotics with ascites; however, it is unknown whet her this increase is caused by increased synthesis or a decrease in th e metabolic processing of these peptides. ANP gene expression in the l iver, atria, ventricles, and gastrointestinal tract of cirrhotic vs. c ontrol rats was studied as was their metabolism. Methods: Sprague-Dawl ey rats developed cirrhosis with ascites approximately 20 weeks after weekly intragastric instillation of carbon tetrachloride. Their circul ating, ascitic, and urinary levels of ANPs were measured by radioimmun oassays. 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 ra ts. ANP gene expression was present but not increased in the liver, at ria, and gastrointestinal tract of cirrhotic rats. No increase of meta bolic processing of these peptides was found in the circulation. Cardi ac ultrasonography and catheterization revealed no ventricular dilatio n or increased ventricular pressure. Conclusions: Elevation of circula ting ANPs with cirrhosis was associated with increased ventricular ste ady-state ANP messenger RNA concentrations. The increased ANP gene exp ression in cirrhosis seems to involve a novel mechanism not related to stretch because neither increased ventricular pressure nor dilation w as present.