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

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 muCi 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 less than 0.05) and urinary volume (4.31 +/- 0.41 vs. 7.57 +/- 0.53 microliter per min; p less than 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 less than 0.05). The opposite was observed for albumin distribution space (34.5 +/- 6.1 vs. 22.1 +/- 3.5%, p less than 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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Volume Expansion on Hemodynamics, Capillary Permeability and Renal Function in Conscious, Cirrhotic Rats

“…In a model of cirrhosis in rats, which closely resembles the human disease in its histological (7) and functional aspects (8), we have demonstrated that cirrhotic animals are unable to excrete adequate amounts of urinary sodium after saline expansion (8,9). Recent data from our laboratory suggested that saline infusion is less effective in increasing intravascular volume in cirrhotic than in control rats, suggesting an inadequate natriuretic response to saline infusion (10).…”

“…Recent data from our laboratory suggested that saline infusion is less effective in increasing intravascular volume in cirrhotic than in control rats, suggesting an inadequate natriuretic response to saline infusion (10).…”

Influence of cardiac function on the diuretic and hemodynamic effects of the loop diuretic piretanide

“…3). Several studies have demonstrated that increased sodium reabsorption occurs predominantly in the proximal renal tubule (Lopez-Novoa et al, 1984;Stein et af., 1974) and that circulating angiotensin I1 and catecholamines play an important role in regulating the percent contribution of the proximal tubule to the total renal sodium reabsorption (Cannon, 1977;Ichikawa et af., 1980Ichikawa et af., , 1984. Increased sodium reabsorption by the distal tubule and collecting duct at high aldosterone activity, also present under conditions of low cardiac index, is less relevant compared to angiotensin I1 avid proximal sodium reabsorption (Chonko et af., 1977).…”