BLUNTED NATRIURETIC RESPONSE TO HUMAN URINE EXTRACTS WITH NA-ATPASE INHIBITING ACTIVITY IN EXPERIMENTAL CIRRHOSIS(, K+)

Human urine and plasma extracts contain a material that inhibits the e nzyme Na+,K+-ATPase (the endogenous sodium pump) and produces natriure sis in the bioassay animal. This endogenous sodium pump inhibitor(s), also known as digitalis-like factor, is thought to be involved in sodi um and extracellular fluid volume homeostasis. Increased urine and pla sma sodium pump inhibiting activity have been reported in patients wit h cirrhosis and sodium retention. The aim of the study was to assess t he renal response to i.v. administration (0.2 ml/min per kg bw for 10 min) of a human urine extract containing sodium pump inhibiting activi ty (28.5 nmol equivalent ouabain/ml) in eight conscious rats with cirr hosis and ascites and eight control rats. Baseline urinary excretion o f Na+,K+-ATPase inhibiting activity was significantly higher in cirrho tic rats with ascites than in control rats (235+/-40 vs 91+/-16; p<0.0 1). Human urine extract induced a significant (p<0.05) increase in glo merular filtration rate in control (3.2+/-0.4 to 4.2+/-0.5 ml/min) and cirrhotic rats (3.0+/-0.3 to 4.0+/-0.5 ml/min). In control rats it al so increased urinary sodium excretion (1.47+/-0.22 to 2.43+/-0.5 mu Eq /min, p<0.01) and fractional sodium excretion (0.29+/-0.01 to 0.43+/-0 .04%, p<0.025). In contrast, in cirrhotic rats with ascites neither so dium excretion nor fractional sodium excretion was significantly affec ted. No changes were observed in plasma aldosterone and atrial natriur etic peptide concentrations in either group. These data suggest that i n cirrhosis there is a renal resistance to the natriuretic effect of e ndogenous sodium pump inhibitor(s). (C) Journal of Hepatology.