Mechanisms of the Impaired Diuretic and Natriuretic Responses to a Sustained and Moderate Saline Infusion in Rats with Experimental Cirrhosis

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Abstract
Kidney function and tubular handling of water and sodium by superficial nephrons, packed cell volume, total plasma proteins and albumin distribution space were studied in control and cirrhotic rats before and after a moderate and sustained saline infusion (3% body weight per 30 min + reposition of urinary losses). Tubular fluid samples were obtained from late proximal, early distal and late distal convolutions of superficial nephrons using micropuncture. Protein distribution was assessed by intravenous injection of 0.5 μCi of (125I)-albumin. In basal conditions, both groups of rats showed similar glomerular filtration rate and renal plasma flow, but cirrhotic animals had lower sodium excretion (fractional excretion of sodium = 0.04 ± 0.01% vs. 0.22 ± 0.02%, p < 0.05) and urinary volume (4.31 ± 0.41 vs. 7.57 ± 0.53 μ1 per min; p < 0.05). After saline infusion, total plasma proteins decreased more in cirrhotic than in control rats (-−18.5 ± 2.7 vs. -12.9 ± 2.2%, p < 0.05). The opposite was observed for albumin distribution space (34.5 ± 6.1 vs. 22.1 ± 3.5%, p < 0.05). Fractional sodium excretion increased to 2.98 ± 0.15% in control rats but only to 0.61 ± 0.080% in cirrhotic rats. The ratio single nephron glomerular filtration rate/glomerular filtration rate increased from 19.6 ± 0.7 to 21.2 ± 1.0 (x10−6, p < 0.005) in control animals but did not change in cirrhotic rats. These animals were unable to decrease adequately fractional fluid reabsorption in the proximal tubule and the loop of Henle. The results suggest that the lack of adequate diuresis and natriuresis after saline infusion in cirrhotic rats depends on lower plasma volume expansion by extravasation of high protein content fluid, lack of intrarenal glomerular filtration rate redistribution, and inadequate decrease in proximal and Henle's loop fluid reabsorption.