Effect of uremia on aldosterone metabolism in the isolated perfused rat liver.

M Egfjord, H Daugaard, K Olgaard

Index: Metab. Clin. Exp. 42(4) , 470-6, (1993)

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Abstract

The effect of uremia on hepatic metabolism of aldosterone was studied in the isolated perfused liver of female Wistar rats. Uremia was induced by five-sixths partial nephrectomy 4 weeks before experiments. Isolated livers of normal and uremic rats were perfused at a constant flow rate with a hemoglobin-free medium, to which 4-14C-D-aldosterone was added at 3 nmol/L. Aldosterone was analyzed by radioimmunoassay (RIA) and 4-14C-D-aldosterone radiometabolites in perfusate and bile were assayed by high-performance liquid chromatography (HPLC). Uremic rats had a 10% lower body weight (P < .01) and increased plasma urea, creatinine, and parathyroid hormone (PTH) levels (258%, 200%, and 208%, respectively; P < .01-.001). Blood pressure and plasma K+, Na+, and aldosterone levels were similar. Plasma renin activity was suppressed by 68% in uremic rats (P < .001). Liver wet weight and hepatic function were similar in livers of both groups of rats. Hepatic elimination of aldosterone was compatible with a first-order kinetics. Hepatic clearance of aldosterone per liver and per gram liver was similar; however, when expressed per 100 g rat body weight, a 21% higher value was observed in uremic rats (11.6 +/- 1.8 mL/min) compared with normal rats (9.6 +/- 1.5 mL/min, P < .01). Polar aldosterone radiometabolites accumulated in the perfusate to approximately 40% of the initial 14C added at 15 minutes, and were eliminated in bile at a similar rate in both groups. No qualitative difference was found in the pattern of radiometabolites of aldosterone in perfusate and bile.(ABSTRACT TRUNCATED AT 250 WORDS)