Renal and Systemic Hemodynamics in Experimental Cirrhosis in Rats: Relation to Hepatic Function

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Abstract
The onset of sodium retention in the phenobarbital and carbon tetrachloride model of cirrhosis in the rat is preceded by a linear decrease in hepatic function as measured by the aminopyrine breath test. Sodium retention occurs when liver function decreases below a critical threshold. Changes in systemic hemodynamics may be responsible for initiating the development of renal sodium retention. The objective of this study was to investigate the relationship between hepatic function and systemic and renal hemodynamics of experimental cirrhosis in rats maintained on a constant salt diet. Cirrhosis was induced in phenobarbitaltreated rats by weekly administration of carbon tetrachloride. The aminopyrine breath test served as a measure of hepatic function. Three groups of animals were studied to evaluate the contribution of changes in systemic and renal hemodynamics to the onset of sodium retention: a group with sodium retention and aminopyrine breath test results just below the critical threshold, a group without sodium retention and aminopyrine breath test results just above the critical threshold and a phenobarbital–treated control group. In each group, urinary sodium excretion, renal plasma flow, glomerular filtration rate, mean arterial pressure and arterial and renal venous plasma renin activities were determined. A progressive, significant reduction in mean arterial pressure was seen, comparing controls with the other two groups. No differences in renal plasma flow were observed between the three groups, but glomerular filtration rate and filtration fraction were slightly reduced in the sodium–retaining group compared with the non–retaining group and controls. A trend toward increased renin activity was observed in both groups of cirrhotic animals, but the differences were not statistically significant, compared with controls. A positive, curvilinear relationship was found between aminopyrine breath test results and mean arterial pressure and glomerular filtration rates, and a negative association was found between aminopyrine breath test results and plasma renin activity. Our data demonstrate, that in carbon tetrachloride-induced cirrhosis in the rat, changes in mean arterial pressure, glomerular filtration rate and plasma renin activity are closely related to the impairment in hepatic function. The significant decrease in mean arterial pressure in nonsodium–retaining cirrhotic rats suggests that peripheral vasodilatation is the initial event in the development of salt retention in this model of cirrhosis. These observations suggest the hypothesis that changes in tubular function, rather than changes in renal hemodynamics and glomerular function, are responsible for the onset of sodium retention. (Hepatology 1990;12:13-19).