SERIAL NATRIURETIC RESPONSE TO ATRIAL PEPTIDE IN PREASCITIC BILE-DUCT LIGATED DOGS

We determined if nine precirrhotic unanaesthetized dogs with chronic bile duct ligation (CBDL) responded uniformly to atrial natriuretic peptide (ANF) by infusing this peptide sequentially over 8-12 weeks at 175 ng·kg-1·min-1 and observing the natriuretic response. ANF was administered every 2 weeks post-CBDL until the 8th week and given again during the cirrhotic phase with ascites present (10-12 weeks post-CBDL). Sodium balance studies were conducted at similar time intervals. During the control period and at weeks, 2, 6, and 8 post-CBDL all dogs responded to ANF with a significant change in sodium excretion (ΔU(Na)V, 50-240 μequiv./min). At these times, all dogs were in sodium balance. At week 4 and during the ascitic period, heterogeneity of response to ANF was observed. In the former interval, five dogs responded (ΔU(Na)V, 75-230 μequiv./min) and four did not, while in the latter interval, five dogs responded (ΔU(Na)V, 50-240 μequiv./min) and three did not (one dog died). In both time periods, there was severe urinary sodium retention (daily U(Na)V, 11 ± 3 and 2 ± 1 mequiv./day, respectively) while the dogs were ingesting 45 mequiv. Na+/day. The heterogeneity of natriuretic response was not correlated to plasma immunoreactive ANF, renin, or aldosterone levels. Plasma volume was significantly expanded from control during both intervals. We conclude that there is transient sodium retention during the 4th week post-CBDL, and that this period is associated with the heterogeneity of natriuretic response to ANF, despite the absence of ascites or edema.