Blunted natriuretic response to human urine extracts with Na+,K(+)-ATPase inhibiting activity in experimental cirrhosis.
Human urine and plasma extracts contain a material that inhibits the enzyme Na+,K(+)-ATPase (the endogenous sodium pump) and produces natriuresis in the bioassay animal. This endogenous sodium pump inhibitor(s), also known as digitalis-like factor, is thought to be involved in sodium and extracellular fluid volume homeostasis. Increased urine and plasma sodium pump inhibiting activity have been reported in patients with cirrhosis and sodium retention. The aim of the study was to assess the 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 activity (28.5 nmol equivalent ouabain/ml) in eight conscious rats with cirrhosis and ascites and eight control rats. Baseline urinary excretion of Na+,K(+)-ATPase inhibiting activity was significantly higher in cirrhotic rats with ascites than in control rats (235 +/- 40 vs 91 +/- 16; p < 0.01). Human urine extract induced a significant (p < 0.05) increase in glomerular 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 also increased urinary sodium excretion (1.47 +/- 0.22 to 2.43 +/- 0.5 microEq/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 sodium excretion nor fractional sodium excretion was significantly affected. No changes were observed in plasma aldosterone and atrial natriuretic peptide concentrations in either group. These data suggest that in cirrhosis there is a renal resistance to the natriuretic effect of endogenous sodium pump inhibitor(s).
Asbert
M
M
Hormonal Laboratory, Hospital Clínic i Provincial, University of Barcelona, Spain.
Clària
J
J
Jiménez
W
W
Arroyo
V
V
Ros
J
J
Gaya
J
J
Rivera
F
F
Rodés
J
J
D000818:Animals; D001794:Blood Pressure; D002251:Carbon Tetrachloride; D005260:Female; D006439:Hemodynamics; D006801:Humans; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000503:physiopathology / Q000652:urine*; D008297:Male; D008875:Middle Aged; D009318:Natriuresis; D010042:Ouabain / Q000652:urine*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D014556:Urine / Q000502:physiology*
C083016:sodium-potassium ATPase inhibitory factor; D010042:Ouabain; D002251:Carbon Tetrachloride; D000254:Sodium-Potassium-Exchanging ATPase