RELATIONSHIP BETWEEN OXIDATIVE HEPATIC-METABOLISM, URINARY SODIUM-EXCRETION AND SYMPATHETIC-NERVE ACTIVITY IN EXPERIMENTAL CIRRHOSIS IN THERAT

This study investigated the relationship between changes in renal symp athetic activity as assessed by renal norepinephrine spillover and the onset of renal sodium retention in the phenobarbital/ carbon tetrachl oride model of experimental cirrhosis in rats. In this model, sodium r etention occurs when hepatic function, assessed by the aminopyrine bre ath test (ABT), falls below a critical threshold. Three groups of rats , studied on a constant salt diet, included a group with cirrhosis and sodium retention, a group with cirrhosis of similar duration and no s odium retention and a time-control phenobarbitaltreated group. ABT, re nal plasma flow (RPF), glomerular filtration rate (GFR) and mean arter ial pressure (MAP) were measured at the time of catecholamine sampling in anesthetized rats. Cirrhosis was associated with reductions in MAP , no change in RPF and GFR, and an ABT below the threshold in rats wit h sodium retention. In contrast, rats without sodium retention had liv er function above the threshold. Renal norepinephrine spillover increa sed continously from controls to non-sodium retaining and sodium retai ning animals. The difference between sodium retaining animals and cont rols was significant. Norepinephrine spillover correlated to ABT and M AP but not urinary salt excretion. The data suggest that, under these experimental conditions, increased sympathetic activity may contribute to the onset of sodium retention. A plausible explanation for the con tinous increase is that catecholamines are released as a compensatory mechanism in response to a primary yet undefined vasodilator.