High plasma cardiac natriuretic peptides associated with enhanced cyclic guanosine monophosphate production in preascitic cirrhosis

Background/Aims: The initial abnormalities of renal sodium handling in cirr hosis remain unclear. The aim of this study was to characterize sodium meta bolism in preascitic cirrhosis. Methods: Ten patients with preascitic cirrhosis and ten controls were studi ed. All subjects ate a diet providing 120 mmol sodium during an equilibrati on period lasting 5 days and the study day. On the study day, after remaini ng in bed, plasma levels of atrial natriuretic peptide, brain natriuretic p eptide, renin activity, aldosterone, noradrenaline, and cyclic guanosine mo nophosphate were measured at 7 am. Thereafter, they were instructed to main tain an upright posture until dinner and the measurements were repeated at 9 am and 6 pm. After having dinner, all subjects were asked to remain in be d and the measurements were repeated at 11 pm. To measure renal sodium and cyclic guanosine monophosphate excretion, 24-h urine collections were perfo rmed, starting from 7 pm on the day before the experimental day. Results: Plasma levels of atrial natriuretic peptide, brain natriuretic pep tide and cyclic guanosine monophosphate in patients with preascitic cirrhos is were significantly elevated compared with those in controls at every sam pling time (p=0.03 or less, p=0.04 or less, and p=0.01 or less). In contras t, plasma renin activities at every sampling time were significantly lower in patients than in controls (p=0.04 or less), Plasma aldosterone and norad renaline levels were not significantly different at every sampling time in the two groups. No significant differences in daily renal sodium excretion were found, However, urinary cyclic guanosine monophosphate excretion was s ignificantly higher in patients than in controls (p<0.01). Conclusions: The initial abnormalities of sodium metabolism in cirrhosis mi ght be characterized by blunted renal responsiveness to natriuretic peptide s. The results of the study also provide indirect evidence that the impairm ent is mainly located at postreceptor levels of signal transduction pathway to the peptides, if the activation of antinatriuretic factors other than r enin-angiotensin or sympathoadrenergic systems does not play a role.